Current topics in complement:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
New York, NY
Springer
2006
|
| Schriftenreihe: | Advances in experimental medicine and biology
586 |
| Schlagworte: | |
| Online-Zugang: | Inhaltstext Inhaltsverzeichnis |
| Beschreibung: | XXII, 406 S. Ill., graph. Darst. |
| ISBN: | 0387322310 9780387322315 |
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| 245 | 1 | 0 | |a Current topics in complement |c [Aegean Conferences]. Ed. by John D. Lambris |
| 264 | 1 | |a New York, NY |b Springer |c 2006 | |
| 300 | |a XXII, 406 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 490 | 1 | |a Advances in experimental medicine and biology |v 586 | |
| 650 | 4 | |a Complément (Immunologie) - Congrès | |
| 650 | 4 | |a Complement (Immunology) |v Congresses | |
| 650 | 4 | |a Complement System Proteins |x immunology |v Congresses | |
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| 689 | 0 | |C b |5 DE-604 | |
| 700 | 1 | |a Lambris, John D. |e Sonstige |4 oth | |
| 830 | 0 | |a Advances in experimental medicine and biology |v 586 |w (DE-604)BV000003102 |9 586 | |
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Datensatz im Suchindex
| _version_ | 1804135571798360064 |
|---|---|
| adam_text | Contents
List of Contributors
.......................................................................................... xvii
1.
Cross-Disciplinary Research Stirs New Challenges into the
Study of the Structure, Function and Systems Biology
of Complement
Dimitrios
Mastellos
and John
D. Lambris
1.
Introduction
.................................................................................................. 1
2.
Biophysical Approaches in Elucidating Complement Structure
and Binding Energetics
................................................................................ 2
3.
Thermodynamics of Complement Protein Binding
...................................... 3
4.
Probing Conformational Changes of Complement Proteins
with Hydrogen/Deuterium Exchange and Mass Spectrometry
..................... 4
5.
Combinatorial and in Silico Protein Design: In Search for
More Potent C3 Inhibitors
............................................................................ 4
6.
Defining the Structural Determinants of Viral Immune Evasion:
The CSb/SPICE/VCP Interaction
................................................................. 6
7.
A Systems Biology Perspective of Innate Immunity:
Newly Identified Crosstalks between Complement and
Divergent Biological Networks
.................................................................... 7
7.1.
Complement Intercepts Cytokine-Driven Regenerative
Networks in the Liver
......................................................................... 9
7.2.
A Complement-Chemokine Crosstalk Regulates
Hematopoietic Stem Cell Engraftment
............................................... 10
7.3.
Complement Modulates Coagulation Processes
................................. 10
8.
Future Perspectives
...................................................................................... 11
9.
Acknowledgments
........................................................................................ 12
10.
References
.................................................................................................... 12
2.
Liver Regeneration: A Link to Inflammation through Complement
Robert A. DeAngelis,
Maciej
M.
Markiewski, and John D.
Lambris
1.
Introduction
.................................................................................................. 17
2.
Liver Regeneration and Inflammatory Mediators
........................................ 18
2.1.
Cytokines and Transcription Factors
.................................................. 19
2.2.
Growth Factors, Metalloproteases, Adhesion Molecules,
and Acute Phase Proteins
.................................................................... 20
2.3.
Natural Killer
T (NKT)
Cells
.............................................................. 22
3.
The Role of Complement in Liver Regeneration
.......................................... 23
4.
Conclusion
................................................................................................... 23
5.
Acknowledgments
........................................................................................ 26
6.
References
.................................................................................................... 26
vii
v¡¡¡
CONTENTS
3.
The Role of Third Complement Component (C3) in Homing
of Hematopoietic Stem/Progenitor Cells into Bone Marrow
Ryan
Reca,
Martin Wysoczynski,
Jun
Yan, John D.
Lambris,
and
Mariusz Z. Ratajczak
1.
Introduction
.................................................................................................. 35
2.
The Function of CXCR4 Receptor Depends on
Lipid
Raft Formation
......... 36
3.
Complement Is Activated in BM during Myeloablative Conditioning
for Hematopoietic Transplantation
............................................................... 37
4.
The Role of Complement in Regulating the Biology of HSPC
.................... 39
5.
Hematopoiesis in CS-Deficient Mice under Normal
Steady-State and Stress Situations
................................................................ 41
6.
Molecular Explanation of the Defect in Homing/Engraftment of
HSPC in CS-Deficient Mice
......................................................................... 42
7.
Conclusions
.................................................................................................. 46
8.
References
.................................................................................................... 46
4.
Complement System and the Eye
Purushottam Jha,
Puran
S.
Bora,
Jeong
-Нуеоп
Sohn,
Henry
J.
Kaplan, and Nalini S. Bora
1.
Introduction
.................................................................................................. 53
2.
Complement and Ocular Protection
............................................................. 54
3.
Complement and Ocular Diseases
................................................................ 54
3.1.
Complement and
Corneal
Diseases
..................................................... 54
3.2.
Complement and Autoimmune Uveitis
............................................... 55
3.3.
Complement and Age-Related
Macular
Degeneration
........................ 55
4.
Complement and Ocular Tolerance
.............................................................. 56
5.
Conclusions
.................................................................................................. 57
6.
References
.................................................................................................... 58
5.
To Regeneration
...
With Complement
Panagiotis A. Tsonis, John
D. Lambris,
and Katia Del Rio-Tsonis
1.
Regenerative Abilities in Vertebrates
........................................................... 63
2.
Limb Regeneration
....................................................................................... 64
3.
Lens Regeneration
........................................................................................ 65
4.
The Complement System
............................................................................. 66
5.
References
.................................................................................................... 68
6.
Self, Non-Self and Danger: A Complementary View
Jörg Kohl
1.
Introduction
.................................................................................................. 71
2.
Complement as a Master Alarm System of Innate Immunity
................... 72
3.
Complement-Derived Danger-Transmitters Shape Innate and
Adaptive Immune Responses following Physiological and
Pathological Threats
..................................................................................... 74
3.1.
Danger Transmission through Clq Receptors
.................................... 75
3.2.
Danger Transmission through C3 Cleavage Fragments
...................... 75
CONTENTS ix
4. Danger Transmission
Mediated through the Anaphylatoxic
Peptides C3a and C5a
................................................................................... 78
4.1.
Anaphylatoxin Receptor-Dependent and -Independent Effects
.......... 79
5.
Anaphylatoxin-Mediated Danger Transmission in Non-Myeloid Cells
....... 81
6.
C5a Receptor Signaling in Pulmonary Dendritic Cells Regulates
Inhalation Tolerance
..................................................................................... 82
7.
C5a Receptor Signaling on APCs Impacts Danger Transmission
through TLRs
............................................................................................... 84
8.
Summary
...................................................................................................... 85
9.
Acknowledgments
........................................................................................ 86
10.
References
.................................................................................................... 86
7.
gClqR
/рЗЗ
Serves as a Molecular Bridge between the
Complement and Contact Activation Systems and Is an
Important Catalyst in Inflammation
Berhane Ghebrehiwet, Claudia Cebada-Mora, Lee Tantral,
Jolyon Jesty, and
Ellinor
I. B. Peerschke
1.
Abstract
........................................................................................................ 95
2.
Introduction
.................................................................................................. 96
3.
Materials and Methods
................................................................................. 97
3.1.
Chemicals and Reagents
..................................................................... 97
3.2.
Proteins and Antibodies
...................................................................... 97
3.3.
Biotinylation of Proteins
..................................................................... 97
3.4.
Expression of
Recombinant
gClqR
.................................................... 98
3.5.
Collection of Normal Human Serum
.................................................. 98
3.6.
Hemolytic Assay
................................................................................. 98
3.7.
Microplate
Assay for Complement Activation
................................... 99
4.
Results
.......................................................................................................... 99
4.1.
Inhibition of Hemolytic Activity by gClqR
....................................... 99
4.2.
Soluble gClqR but not
Δ74-96
gClqR Can Activate
the Classical Pathway
......................................................................... 100
5.
Discussion
.................................................................................................... 101
6.
Acknowledgments
........................................................................................ 103
7.
References
.................................................................................................... 104
8.
Possible Immunoprotective and Angiogenesis-Promoting
Roles for Malignant Cell-Derived Prostasomes: A New
Paradigm for
Prestatie
Cancer?
Kristina Nilsson Ekdahl, Gunnar Ronquist, Bo Nilsson,
and
Adii
A. Babiker
1.
Introduction
.................................................................................................. 107
2.
Hypothesis: Malignant Cell-Derived Prostasomes Provide Cancer
Cells with a Zone of Innate Immune Privilege
............................................. 109
3.
Complement Activation and Expression of Complement Regulatory
Proteins by Malignant Cells
......................................................................... 110
4.
CD59 Transfer by Prostasomes Results in Protection against
Complement-Mediated Lysis
....................................................................... 111
5.
Extracellular Phosphorylation of Plasma Proteins
........................................ 113
x
CONTENTS
6.
Mapping of Protein Kinases on Prostasomes
............................................... 114
7.
C3 and other Substrates for Prostasomal PKs
.............................................. 115
8.
Conclusions
.................................................................................................. 116
9.
References
.................................................................................................... 116
9.
Diversified Components of the Bony Fish Complement System:
More Genes for
Robuster
Innate Defense?
Miki
Nakao, Yoko Kato-Unoki, Makiko Nakahara,
Junichi Mutsuro, and Tomonori Somamoto
1.
Introduction
.................................................................................................. 121
2.
Classical Pathway Components
.................................................................... 123
3.
Lectin Pathway Components
........................................................................ 125
4.
Alternative Pathway Components
................................................................ 126
5.
Lytic Pathway Components
.......................................................................... 131
6.
Complement Receptors
................................................................................ 131
7.
Regulatory Factors
....................................................................................... 132
8.
Concluding Remarks and Future Directions
................................................. 133
9.
Acknowledgments
........................................................................................ 134
10.
References
.................................................................................................... 134
10.
C5b-9
Complement Complex in Autoimmune Demyelination:
Dual Role in
Neuroinflammation
and
Neuroprotection
Horea
Rus,
Cornelia
Cudria,
and Florin Niculescu
1.
Introduction
.................................................................................................. 139
2.
Role of CSb-9 in
Neuroinflammation
........................................................... 140
2.1.
In Vitro Demyelination by
C5b-9
....................................................... 140
2.2.
Role of CSb-9 in Demyelination during EAE
..................................... 141
3.
Role of CSb-9 in
Neuroprotection
................................................................ 142
3.1.
Inhibition of Oligodendrocyte Apoptosis by Sublytic C5b-9
.............. 142
3.2.
Contribution of Complement C5 to
Neuroprotection
in EAE
............. 145
4.
Does
СбЬ^
Protect Oligodendrocytes from Apoptosis in
Multiple Sclerosis?
....................................................................................... 146
5.
Acknowledgments
........................................................................................ 148
6.
References
.................................................................................................... 148
11.
The Double-Edged Flower: Roles of Complement Protein Clq
in
Neurodegenerative
Diseases
Andrea J. Tenner and Maria I.
Fonseca
1.
Introduction
.................................................................................................. 153
2.
Complement in the Brain
............................................................................. 155
3.
Murine
Models of Alzheimer s Disease
........................................................ 157
4.
Potential Protective Roles of Complement in the CNS
................................ 162
5.
Potential Complement-Based Therapeutics
.................................................. 165
6.
Summary
...................................................................................................... 166
7.
Acknowledgments
........................................................................................ 166
8.
References
.................................................................................................... 167
CONTENTS Xi
12.
The Role of the Complement System in the Pathogenesis
of Experimental Autoimmune Encephalomyelitis and
Multiple Sclerosis
Nóra
Terény i,
József Prechl, and Anna Erdei
1.
Introduction
.................................................................................................. 177
2.
Local Production as a Complement Source in the CNS
............................... 180
3.
The Role of Complement Deposition in
Myelin
Damage
............................ 180
3.1.
Decomplementation by
CVF.............................................................. 180
3.2.
Cl.......................................................................................................
182
3.3.
СЗ
....................................................................................................... 182
3.4.
C4
....................................................................................................... 182
3.5.
C5
....................................................................................................... 183
3.6.
C6-C9,
МАС
...................................................................................... 183
4.
Anaphylatoxin Effects in Demyelinization
.................................................. 183
5.
Complement Regulation in the CNS
............................................................ 185
6.
Complement and Therapy of EAE
............................................................... 185
7.
Acknowledgments
........................................................................................ 186
8.
References
.................................................................................................... 186
13.
The Complement System: A Potential Target for Stroke Therapy
J.
Moceo,
Michael E. Sughrue, Andrew F. Ducruet,
Ricardo
J.
Kotnotar,
Sergei A. Sosunov, and
E.
Sander Connolly Jr.
1.
Introduction
.................................................................................................. 189
2.
Rationale for Blocking Complement Activation to Treat Stroke
.................. 190
2.1.
Inflammation Is Deleterious in Stroke, and Complement Is
Activated in Stroke
............................................................................. 190
2.2.
Complement Activation Exacerbates
Ischemie
Injury in
Other Organs
....................................................................................... 191
2.3.
Complement Activation Causes Injury in Other Nervous
System Diseases
.................................................................................. 191
2.4.
Neurons Seem to Be Unusually Susceptible to
Complement Activation
...................................................................... 191
2.5.
In Vivo Evidence Suggests that Complement Is Involved
in Cerebral I/R Pathogenesis
............................................................... 192
3.
Potential Negatives of Complement Blockade following Stroke
................. 193
3.1.
Complement May Be Needed to Opsonize Cellular
Debris after Stroke
.............................................................................. 194
3.2.
Complement Aids Tissue Recovery/Repair in Other Organs
.............. 194
3.3.
Complement Activation Products May Be Neuroprotective
............... 195
4.
Conclusion
................................................................................................... 195
5.
References
.................................................................................................... 195
14.
Observations on Complement Activity in the Two-Stage
Inflammatory/Hemostatic Response in the Baboon and
Human Models off.
Coli
Sepsis and Endotoxemia
Fletcher B. Taylor Jr., Eric Hack, and
Florea
Lupu
1.
Introduction
.................................................................................................. 203
xii CONTENTS
2.
Description
of the Baboon and Human Models of
E. Coli
Sepsis
and Endotoxemia
.......................................................................................... 204
2.1.
Baboon
E. Coli
Sepsis Model
............................................................. 204
2.2.
Human Endotoxin Model
.................................................................... 204
3.
Results
.......................................................................................................... 206
3.1.
Activation Parameters of the Complement System in
Baboons after Lethal and Sublethal
E. Coli
Challenge
....................... 206
3.2.
Activation Parameters of Cytokine Complement and
Hemostatic
Systems in Humans after Endotoxin
Challenge: Evidence Establishing Two Distinct
Sequential Pathophysiologic Events
................................................... 208
3.3.
Evidence Suggesting that There Is a Unique
Counterpart to the Second Stage of the
Compensated Response to
E. Coli
that Is Distinct
from the Lethal Counterpart to the First Stage
.................................... 210
4.
Conclusions
.................................................................................................. 210
5.
References
.................................................................................................... 215
15.
Complement Activation during Sepsis in Humans
Heike Schreiber,
Daniel Rittirsch, Michael
Flierl,
Uwe Brueckner,
Marion Schneider, Manfred Weiss,
Florian Gebhard,
and
Markus Huber-Lang
1.
Introduction
.................................................................................................. 217
2.
Material and Methods
................................................................................... 218
2.1.
Reagents
............................................................................................. 218
2.2.
Patient Selection
................................................................................. 218
2.3.
Measurement of Serum Concentrations of
C3a, C5a, and MAC
............................................................................ 219
2.4.
Hemolytic Complement Assay
........................................................... 219
2.5.
Neutrophil Isolation
............................................................................ 219
2.6.
Analysis of C5aR Content on Neutrophils
.......................................... 219
2.7.
Statistical Analysis
.............................................................................. 220
3.
Results
.......................................................................................................... 220
3.1.
Epidemiological Assessments
............................................................. 220
3.2.
Sepsis-Induced Complement Activation during
Septic Shock in Humans
..................................................................... 220
3.3.
Sepsis-Induced Impairment of Complement Function
during Septic Shock in Humans
.......................................................... 221
3.4.
Loss of C5aR on Neutrophils Is Associated with a
Lethal Outcome during Sepsis in Humans
.......................................... 221
4.
Discussion
.................................................................................................... 222
5.
Acknowledgments
........................................................................................ 224
6.
References
.................................................................................................... 225
CONTENTS xiii
16.
Three Distinct Profiles of Serum Complement C4 Proteins
in
Pediatrie
Systemic Lupus Erythematosus (SLE) Patients:
Tight Associations of Complement C4 and C3 Protein Levels
in SLE but not in Healthy Subjects
Yee-Ling Wu, Gloria
С
Higgins, Robert M. Rennebohm,
Erwin K.
Chung, Yan Yang, Bi Zhou, Haikady
N.
Nagaraja,
Dan J. Birmingham, Brad H.
Rovin,
Lee A.
Hebert,
and C. Yung Yu
1.
Abstract
........................................................................................................ 227
2.
Introduction
.................................................................................................. 228
3.
Materials and Methods
................................................................................. 229
3.1.
Study Populations
............................................................................... 229
3.2.
Preparation of EDTA-Plasma and Genomic DNAs
............................ 229
3.3.
C4 Phenotyping and Genotyping
........................................................ 229
3.4.
Mutations of Complement C4 and C2 Genes
...................................... 230
3.5.
Clinical Information
............................................................................ 230
3.6.
Statistics
.............................................................................................. 230
4.
Results
.......................................................................................................... 230
4.1.
Demographics and Clinical Features of the
Pediatrie
SLE Study Population
......................................................................... 23
1
4.2.
Three Types of C3-C4 Protein Profiles in SLE Patients
.................... 233
4.3.
Tight Correlation between Serum C3 and C4 Concentrations
in SLE Patients but not in Healthy Subjects
....................................... 233
4.4.
Serum C3 and C4 Levels Both Correlated
BMI
but
BMI
Alone Could not Account for the Tight
Association between Serum C3 and C4 Levels
.................................. 238
4.5.
C4
Genotypie
and Phenotypic Variations in
Pediatrie SLE
................ 239
4.6.
C4 Gene Dosage Is a Determinant of the Maximum
Serum C4 Concentrations in
Pediatrie SLE
........................................ 241
5.
Discussion
.................................................................................................... 242
6.
Acknowledgments
........................................................................................ 244
7.
References
.................................................................................................... 244
17.
A Minimum CR2 Binding Domain of C3d Enhances
Immunity following Vaccination
Joseph F. Bower and Ted M. Ross
1.
Abstract
........................................................................................................ 249
2.
Introduction
.................................................................................................. 250
3.
Materials and Methods
................................................................................. 251
3.1.
PlasmidDNA
...................................................................................... 251
3.2.
Purification of
Recombinant
Protein Antigens
................................... 251
3.3.
Protein Expression
.............................................................................. 252
3.4.
Animals and Immunizations
............................................................... 252
3.5.
ELISA
................................................................................................. 253
3.6.
ELISpot
............................................................................................... 253
3.7.
Statistical Analysis
.............................................................................. 254
4.
Results
.......................................................................................................... 254
4.1.
Expression of Vaccine Plasmids
......................................................... 254
Xiv CONTENTS
4.2.
Cell-Mediated
Immune
Responses Elicited by Env-mCSd,
................ 255
4.3.
Anti-Env Antibody Responses
............................................................ 256
4.4.
Mucosal Immunizations
...................................................................... 256
5.
Discussion
.................................................................................................... 258
6.
Acknowledgments
........................................................................................ 260
7.
References
.................................................................................................... 260
18.
Structure and Function of Ficolins
Yuichi Endo, Yu Liu, and Teizo Fujita
1.
Introduction
.................................................................................................. 265
2.
Structure of Ficolin
...................................................................................... 266
3.
Tissue and Cell Type Expressing Ficolin
..................................................... 268
4.
Phylogeny of the Ficolin Family
.................................................................. 269
5.
Function of Ficolin
....................................................................................... 271
5.1.
Carbohydrate Binding of Ficolin
........................................................ 271
5.2.
Binding of Ficolin to Bacteria
............................................................. 271
5.3.
Ficolin as a Recognition Molecule in the Lectin Pathway
.................. 274
6.
Polymorphisms of the Ficolin Gene
............................................................. 275
7.
Conclusions
.................................................................................................. 275
8.
Acknowledgments
........................................................................................ 276
9.
References
.................................................................................................... 276
19.
Role of Mannose-Binding Lectin (MBL2) Genotyping in
Predicting the Risk of Recurrent
Otitis
Media (rOM)
Lieve
Nuytinck,
Els De Meester,
Martine
Van
Thielen,
and Paul Govaerts
1.
Introduction
.................................................................................................. 281
2.
MBL2 Gene and Polymorphisms
.................................................................. 283
3.
Materials and Methods
................................................................................. 284
3.1.
Patients and Controls
.......................................................................... 284
3.2.
MBL2 Genotyping
.............................................................................. 285
4.
Results
.......................................................................................................... 285
5.
Discussion
.................................................................................................... 286
6.
References
.................................................................................................... 289
20.
Conformational Complexity of Complement Component C3
Bert J. C.
Janssen
and
Piet
Gros
1.
Introduction
.................................................................................................. 291
2.
Structural Organization of C3
...................................................................... 292
3.
Convertase Formation
.................................................................................. 296
4.
Decay Acceleration
...................................................................................... 299
5.
Cofactor Activity
.......................................................................................... 301
6.
Signaling Roles of C3B Fragments
.............................................................. 302
7.
Concluding Remarks
.................................................................................... 303
8.
Acknowledgments
........................................................................................ 304
9.
References
.................................................................................................... 304
CONTENTS xv
21. Disease-Associated
Sequence Variations in Factor
H:
A Structural
Biology Approach
Andrew P. Herbert, Dinesh C.
Soares,
Michael
К.
Pangburn,
and Paul
N.
Barlow
1.
Introduction
.................................................................................................. 313
2.
Regulation of the Complement System
........................................................ 314
3.
Factor
H
....................................................................................................... 315
4.
Functional Sites of Factor
H
......................................................................... 317
5.
Atypical Hemolytic
Uremie
Syndrome
........................................................ 318
6.
Age-Related
Macular
Degeneration
............................................................. 318
7.
Modeled Modules of Factor
H
..................................................................... 319
8.
Predicted Structural Consequences of Amino-Acid Substitutions
................ 321
9.
References
.................................................................................................... 323
22. Transdermal
Pharmacology of Small Molecule Cyclic
C5a Antagonists
Lavinia M. Proctor, Trent M. Woodruff, Prakirti Sharma,
Ian A. Shiels, and Stephen M. Taylor
1.
Abstract
........................................................................................................ 329
2.
Introduction
.................................................................................................. 330
3.
Material and Methods
................................................................................... 332
3.1.
Materials
............................................................................................. 332
3.2.
Isolation of Polymorphonuclear Leukocytes
....................................... 332
3.3.
Receptor Binding Assay
..................................................................... 333
3.4
Myeloperoxidase Release from PMNs
................................................ 333
3.5.
In Vivo Studies
................................................................................... 333
3.6.
Statistical Analysis
.............................................................................. 334
4.
Results
.......................................................................................................... 335
4.1.
In Vitro Activity of PMX Compounds
................................................ 335
4.2. Transdermal
Pharmacokinetics of Cyclic C5a
Receptor Antagonists
.......................................................................... 335
4.3.
Effect of Administration of C5a Antagonists on
LPS-Induced Neutropenia and Hypotension
....................................... 337
5.
Discussion
.................................................................................................... 341
6.
References
.................................................................................................... 342
23.
Inactivation of Complement by
Recombinant
Human
C3 Derivatives
Edzard
Spillner,
Johanna
Kölln,
and
Reinhard Bredehorst
1.
Introduction
.................................................................................................. 347
2.
Generation of
CVF
Chimeras and C3 Derivatives
....................................... 349
3.
Functional Characteristics of the C3 Derivatives
......................................... 351
4.
The C345C Domain in Complement
............................................................ 353
5.
Therapeutical Implications
........................................................................... 355
6.
Conclusions
.................................................................................................. 356
7.
References
.................................................................................................... 356
xvi CONTENTS
24.
Complement
Analysis in Clinic and Research
Tom E. Mollnes and Michael
Kirschfink
1.
Introduction
.................................................................................................. 361
1.1.
The Complement System
.................................................................... 361
2.
Clinical Indications for Complement Analysis
............................................. 363
2.1.
Recurrent Infections
............................................................................ 364
2.2.
Autoimmune Diseases
........................................................................ 365
2.3.
Membranoproliferative Glomerulonephritis (MPGN)
and Hemolytic
Uremie
Syndrome
(HUS)
........................................... 365
2.4.
Hereditary Angioedema
...................................................................... 366
2.5.
Paroxysmal Nocturnal Hemoglobinuria (PNH)
.................................. 366
3.
Complement Tests
........................................................................................ 366
3.1.
Functional Assays
............................................................................... 366
3.2.
Protein Quantification of Individual Components
.............................. 370
3.3.
Genetic Analysis
................................................................................. 370
3.4.
Cell Surface Expression of Complement Proteins
.............................. 370
3.5.
Analysis of Complement Activation Products
.................................... 370
4.
Complement Analysis in Experimental Settings
.......................................... 372
4.1.
In Vitro Experiments with Human Serum and Blood
......................... 372
4.2.
Animal Experiments
........................................................................... 373
5.
Outlook
........................................................................................................ 375
6.
References
.................................................................................................... 375
25.
Cell-Bound Complement Activation Products (CB-CAPs)
as a Source of Lupus
Biomarkers
Sarah J.
Calano,
Pei-an B. Shih, Chau-Ching Liu, Amy H.
Kao,
Jeannine
S. Navrátil,
Susan
Manzi,
and Joseph M. Ahearn
1.
Introduction
.................................................................................................. 381
2.
Measurement of Complement in SLE
.......................................................... 382
2.1.
Serum C3 and C4 and SLE Disease Activity
...................................... 382
2.2.
Issues Associated with Measuring Soluble
........................................
Complement Components
................................................................... 382
2.3.
Complement Activation Products and SLE Disease Activity
............. 384
3.
Cell-Bound Complement Activation Products
............................................. 384
3.1.
Erythrocyte-Bound C4d as a Diagnostic Assay for SLE
..................... 385
3.2.
Reticulocyte-Bound C4d as an Instant Messenger of
Disease Activity in SLE
...................................................................... 387
4.
Summary
...................................................................................................... 387
5.
Acknowledgments
........................................................................................ 388
6.
References
.................................................................................................... 388
Author Index
....................................................................................................... 391
Subject Index
...................................................................................................... 393
|
| adam_txt |
Contents
List of Contributors
. xvii
1.
Cross-Disciplinary Research Stirs New Challenges into the
Study of the Structure, Function and Systems Biology
of Complement
Dimitrios
Mastellos
and John
D. Lambris
1.
Introduction
. 1
2.
Biophysical Approaches in Elucidating Complement Structure
and Binding Energetics
. 2
3.
Thermodynamics of Complement Protein Binding
. 3
4.
Probing Conformational Changes of Complement Proteins
with Hydrogen/Deuterium Exchange and Mass Spectrometry
. 4
5.
Combinatorial and in Silico Protein Design: In Search for
More Potent C3 Inhibitors
. 4
6.
Defining the Structural Determinants of Viral Immune Evasion:
The CSb/SPICE/VCP Interaction
. 6
7.
A "Systems Biology" Perspective of Innate Immunity:
Newly Identified "Crosstalks" between Complement and
Divergent Biological Networks
. 7
7.1.
Complement Intercepts Cytokine-Driven Regenerative
Networks in the Liver
. 9
7.2.
A Complement-Chemokine "Crosstalk" Regulates
Hematopoietic Stem Cell Engraftment
. 10
7.3.
Complement Modulates Coagulation Processes
. 10
8.
Future Perspectives
. 11
9.
Acknowledgments
. 12
10.
References
. 12
2.
Liver Regeneration: A Link to Inflammation through Complement
Robert A. DeAngelis,
Maciej
M.
Markiewski, and John D.
Lambris
1.
Introduction
. 17
2.
Liver Regeneration and Inflammatory Mediators
. 18
2.1.
Cytokines and Transcription Factors
. 19
2.2.
Growth Factors, Metalloproteases, Adhesion Molecules,
and Acute Phase Proteins
. 20
2.3.
Natural Killer
T (NKT)
Cells
. 22
3.
The Role of Complement in Liver Regeneration
. 23
4.
Conclusion
. 23
5.
Acknowledgments
. 26
6.
References
. 26
vii
v¡¡¡
CONTENTS
3.
The Role of Third Complement Component (C3) in Homing
of Hematopoietic Stem/Progenitor Cells into Bone Marrow
Ryan
Reca,
Martin Wysoczynski,
Jun
Yan, John D.
Lambris,
and
Mariusz Z. Ratajczak
1.
Introduction
. 35
2.
The Function of CXCR4 Receptor Depends on
Lipid
Raft Formation
. 36
3.
Complement Is Activated in BM during Myeloablative Conditioning
for Hematopoietic Transplantation
. 37
4.
The Role of Complement in Regulating the Biology of HSPC
. 39
5.
Hematopoiesis in CS-Deficient Mice under Normal
Steady-State and Stress Situations
. 41
6.
Molecular Explanation of the Defect in Homing/Engraftment of
HSPC in CS-Deficient Mice
. 42
7.
Conclusions
. 46
8.
References
. 46
4.
Complement System and the Eye
Purushottam Jha,
Puran
S.
Bora,
Jeong
-Нуеоп
Sohn,
Henry
J.
Kaplan, and Nalini S. Bora
1.
Introduction
. 53
2.
Complement and Ocular Protection
. 54
3.
Complement and Ocular Diseases
. 54
3.1.
Complement and
Corneal
Diseases
. 54
3.2.
Complement and Autoimmune Uveitis
. 55
3.3.
Complement and Age-Related
Macular
Degeneration
. 55
4.
Complement and Ocular Tolerance
. 56
5.
Conclusions
. 57
6.
References
. 58
5.
To Regeneration
.
With Complement
Panagiotis A. Tsonis, John
D. Lambris,
and Katia Del Rio-Tsonis
1.
Regenerative Abilities in Vertebrates
. 63
2.
Limb Regeneration
. 64
3.
Lens Regeneration
. 65
4.
The Complement System
. 66
5.
References
. 68
6.
Self, Non-Self and Danger: A Complementary View
Jörg Kohl
1.
Introduction
. 71
2.
Complement as a "Master Alarm System" of Innate Immunity
. 72
3.
Complement-Derived Danger-Transmitters Shape Innate and
Adaptive Immune Responses following Physiological and
Pathological Threats
. 74
3.1.
Danger Transmission through Clq Receptors
. 75
3.2.
Danger Transmission through C3 Cleavage Fragments
. 75
CONTENTS ix
4. Danger Transmission
Mediated through the Anaphylatoxic
Peptides C3a and C5a
. 78
4.1.
Anaphylatoxin Receptor-Dependent and -Independent Effects
. 79
5.
Anaphylatoxin-Mediated Danger Transmission in Non-Myeloid Cells
. 81
6.
C5a Receptor Signaling in Pulmonary Dendritic Cells Regulates
Inhalation Tolerance
. 82
7.
C5a Receptor Signaling on APCs Impacts Danger Transmission
through TLRs
. 84
8.
Summary
. 85
9.
Acknowledgments
. 86
10.
References
. 86
7.
gClqR
/рЗЗ
Serves as a Molecular Bridge between the
Complement and Contact Activation Systems and Is an
Important Catalyst in Inflammation
Berhane Ghebrehiwet, Claudia Cebada-Mora, Lee Tantral,
Jolyon Jesty, and
Ellinor
I. B. Peerschke
1.
Abstract
. 95
2.
Introduction
. 96
3.
Materials and Methods
. 97
3.1.
Chemicals and Reagents
. 97
3.2.
Proteins and Antibodies
. 97
3.3.
Biotinylation of Proteins
. 97
3.4.
Expression of
Recombinant
gClqR
. 98
3.5.
Collection of Normal Human Serum
. 98
3.6.
Hemolytic Assay
. 98
3.7.
Microplate
Assay for Complement Activation
. 99
4.
Results
. 99
4.1.
Inhibition of Hemolytic Activity by gClqR
. 99
4.2.
Soluble gClqR but not
Δ74-96
gClqR Can Activate
the Classical Pathway
. 100
5.
Discussion
. 101
6.
Acknowledgments
. 103
7.
References
. 104
8.
Possible Immunoprotective and Angiogenesis-Promoting
Roles for Malignant Cell-Derived Prostasomes: A New
Paradigm for
Prestatie
Cancer?
Kristina Nilsson Ekdahl, Gunnar Ronquist, Bo Nilsson,
and
Adii
A. Babiker
1.
Introduction
. 107
2.
Hypothesis: Malignant Cell-Derived Prostasomes Provide Cancer
Cells with a Zone of Innate Immune Privilege
. 109
3.
Complement Activation and Expression of Complement Regulatory
Proteins by Malignant Cells
. 110
4.
CD59 Transfer by Prostasomes Results in Protection against
Complement-Mediated Lysis
. 111
5.
Extracellular Phosphorylation of Plasma Proteins
. 113
x
CONTENTS
6.
Mapping of Protein Kinases on Prostasomes
. 114
7.
C3 and other Substrates for Prostasomal PKs
. 115
8.
Conclusions
. 116
9.
References
. 116
9.
Diversified Components of the Bony Fish Complement System:
More Genes for
Robuster
Innate Defense?
Miki
Nakao, Yoko Kato-Unoki, Makiko Nakahara,
Junichi Mutsuro, and Tomonori Somamoto
1.
Introduction
. 121
2.
Classical Pathway Components
. 123
3.
Lectin Pathway Components
. 125
4.
Alternative Pathway Components
. 126
5.
Lytic Pathway Components
. 131
6.
Complement Receptors
. 131
7.
Regulatory Factors
. 132
8.
Concluding Remarks and Future Directions
. 133
9.
Acknowledgments
. 134
10.
References
. 134
10.
C5b-9
Complement Complex in Autoimmune Demyelination:
Dual Role in
Neuroinflammation
and
Neuroprotection
Horea
Rus,
Cornelia
Cudria,
and Florin Niculescu
1.
Introduction
. 139
2.
Role of CSb-9 in
Neuroinflammation
. 140
2.1.
In Vitro Demyelination by
C5b-9
. 140
2.2.
Role of CSb-9 in Demyelination during EAE
. 141
3.
Role of CSb-9 in
Neuroprotection
. 142
3.1.
Inhibition of Oligodendrocyte Apoptosis by Sublytic C5b-9
. 142
3.2.
Contribution of Complement C5 to
Neuroprotection
in EAE
. 145
4.
Does
СбЬ^
Protect Oligodendrocytes from Apoptosis in
Multiple Sclerosis?
. 146
5.
Acknowledgments
. 148
6.
References
. 148
11.
The Double-Edged Flower: Roles of Complement Protein Clq
in
Neurodegenerative
Diseases
Andrea J. Tenner and Maria I.
Fonseca
1.
Introduction
. 153
2.
Complement in the Brain
. 155
3.
Murine
Models of Alzheimer's Disease
. 157
4.
Potential Protective Roles of Complement in the CNS
. 162
5.
Potential Complement-Based Therapeutics
. 165
6.
Summary
. 166
7.
Acknowledgments
. 166
8.
References
. 167
CONTENTS Xi
12.
The Role of the Complement System in the Pathogenesis
of Experimental Autoimmune Encephalomyelitis and
Multiple Sclerosis
Nóra
Terény i,
József Prechl, and Anna Erdei
1.
Introduction
. 177
2.
Local Production as a Complement Source in the CNS
. 180
3.
The Role of Complement Deposition in
Myelin
Damage
. 180
3.1.
Decomplementation by
CVF. 180
3.2.
Cl.
182
3.3.
СЗ
. 182
3.4.
C4
. 182
3.5.
C5
. 183
3.6.
C6-C9,
МАС
. 183
4.
Anaphylatoxin Effects in Demyelinization
. 183
5.
Complement Regulation in the CNS
. 185
6.
Complement and Therapy of EAE
. 185
7.
Acknowledgments
. 186
8.
References
. 186
13.
The Complement System: A Potential Target for Stroke Therapy
J.
Moceo,
Michael E. Sughrue, Andrew F. Ducruet,
Ricardo
J.
Kotnotar,
Sergei A. Sosunov, and
E.
Sander Connolly Jr.
1.
Introduction
. 189
2.
Rationale for Blocking Complement Activation to Treat Stroke
. 190
2.1.
Inflammation Is Deleterious in Stroke, and Complement Is
Activated in Stroke
. 190
2.2.
Complement Activation Exacerbates
Ischemie
Injury in
Other Organs
. 191
2.3.
Complement Activation Causes Injury in Other Nervous
System Diseases
. 191
2.4.
Neurons Seem to Be Unusually Susceptible to
Complement Activation
. 191
2.5.
In Vivo Evidence Suggests that Complement Is Involved
in Cerebral I/R Pathogenesis
. 192
3.
Potential Negatives of Complement Blockade following Stroke
. 193
3.1.
Complement May Be Needed to Opsonize Cellular
Debris after Stroke
. 194
3.2.
Complement Aids Tissue Recovery/Repair in Other Organs
. 194
3.3.
Complement Activation Products May Be Neuroprotective
. 195
4.
Conclusion
. 195
5.
References
. 195
14.
Observations on Complement Activity in the Two-Stage
Inflammatory/Hemostatic Response in the Baboon and
Human Models off.
Coli
Sepsis and Endotoxemia
Fletcher B. Taylor Jr., Eric Hack, and
Florea
Lupu
1.
Introduction
. 203
xii CONTENTS
2.
Description
of the Baboon and Human Models of
E. Coli
Sepsis
and Endotoxemia
. 204
2.1.
Baboon
E. Coli
Sepsis Model
. 204
2.2.
Human Endotoxin Model
. 204
3.
Results
. 206
3.1.
Activation Parameters of the Complement System in
Baboons after Lethal and Sublethal
E. Coli
Challenge
. 206
3.2.
Activation Parameters of Cytokine Complement and
Hemostatic
Systems in Humans after Endotoxin
Challenge: Evidence Establishing Two Distinct
Sequential Pathophysiologic Events
. 208
3.3.
Evidence Suggesting that There Is a Unique
Counterpart to the Second Stage of the
Compensated Response to
E. Coli
that Is Distinct
from the Lethal Counterpart to the First Stage
. 210
4.
Conclusions
. 210
5.
References
. 215
15.
Complement Activation during Sepsis in Humans
Heike Schreiber,
Daniel Rittirsch, Michael
Flierl,
Uwe Brueckner,
Marion Schneider, Manfred Weiss,
Florian Gebhard,
and
Markus Huber-Lang
1.
Introduction
. 217
2.
Material and Methods
. 218
2.1.
Reagents
. 218
2.2.
Patient Selection
. 218
2.3.
Measurement of Serum Concentrations of
C3a, C5a, and MAC
. 219
2.4.
Hemolytic Complement Assay
. 219
2.5.
Neutrophil Isolation
. 219
2.6.
Analysis of C5aR Content on Neutrophils
. 219
2.7.
Statistical Analysis
. 220
3.
Results
. 220
3.1.
Epidemiological Assessments
. 220
3.2.
Sepsis-Induced Complement Activation during
Septic Shock in Humans
. 220
3.3.
Sepsis-Induced Impairment of Complement Function
during Septic Shock in Humans
. 221
3.4.
Loss of C5aR on Neutrophils Is Associated with a
Lethal Outcome during Sepsis in Humans
. 221
4.
Discussion
. 222
5.
Acknowledgments
. 224
6.
References
. 225
CONTENTS xiii
16.
Three Distinct Profiles of Serum Complement C4 Proteins
in
Pediatrie
Systemic Lupus Erythematosus (SLE) Patients:
Tight Associations of Complement C4 and C3 Protein Levels
in SLE but not in Healthy Subjects
Yee-Ling Wu, Gloria
С
Higgins, Robert M. Rennebohm,
Erwin K.
Chung, Yan Yang, Bi Zhou, Haikady
N.
Nagaraja,
Dan J. Birmingham, Brad H.
Rovin,
Lee A.
Hebert,
and C. Yung Yu
1.
Abstract
. 227
2.
Introduction
. 228
3.
Materials and Methods
. 229
3.1.
Study Populations
. 229
3.2.
Preparation of EDTA-Plasma and Genomic DNAs
. 229
3.3.
C4 Phenotyping and Genotyping
. 229
3.4.
Mutations of Complement C4 and C2 Genes
. 230
3.5.
Clinical Information
. 230
3.6.
Statistics
. 230
4.
Results
. 230
4.1.
Demographics and Clinical Features of the
Pediatrie
SLE Study Population
. 23
1
4.2.
Three Types of C3-C4 Protein Profiles in SLE Patients
. 233
4.3.
Tight Correlation between Serum C3 and C4 Concentrations
in SLE Patients but not in Healthy Subjects
. 233
4.4.
Serum C3 and C4 Levels Both Correlated
BMI
but
BMI
Alone Could not Account for the Tight
Association between Serum C3 and C4 Levels
. 238
4.5.
C4
Genotypie
and Phenotypic Variations in
Pediatrie SLE
. 239
4.6.
C4 Gene Dosage Is a Determinant of the Maximum
Serum C4 Concentrations in
Pediatrie SLE
. 241
5.
Discussion
. 242
6.
Acknowledgments
. 244
7.
References
. 244
17.
A Minimum CR2 Binding Domain of C3d Enhances
Immunity following Vaccination
Joseph F. Bower and Ted M. Ross
1.
Abstract
. 249
2.
Introduction
. 250
3.
Materials and Methods
. 251
3.1.
PlasmidDNA
. 251
3.2.
Purification of
Recombinant
Protein Antigens
. 251
3.3.
Protein Expression
. 252
3.4.
Animals and Immunizations
. 252
3.5.
ELISA
. 253
3.6.
ELISpot
. 253
3.7.
Statistical Analysis
. 254
4.
Results
. 254
4.1.
Expression of Vaccine Plasmids
. 254
Xiv CONTENTS
4.2.
Cell-Mediated
Immune
Responses Elicited by Env-mCSd,
. 255
4.3.
Anti-Env Antibody Responses
. 256
4.4.
Mucosal Immunizations
. 256
5.
Discussion
. 258
6.
Acknowledgments
. 260
7.
References
. 260
18.
Structure and Function of Ficolins
Yuichi Endo, Yu Liu, and Teizo Fujita
1.
Introduction
. 265
2.
Structure of Ficolin
. 266
3.
Tissue and Cell Type Expressing Ficolin
. 268
4.
Phylogeny of the Ficolin Family
. 269
5.
Function of Ficolin
. 271
5.1.
Carbohydrate Binding of Ficolin
. 271
5.2.
Binding of Ficolin to Bacteria
. 271
5.3.
Ficolin as a Recognition Molecule in the Lectin Pathway
. 274
6.
Polymorphisms of the Ficolin Gene
. 275
7.
Conclusions
. 275
8.
Acknowledgments
. 276
9.
References
. 276
19.
Role of Mannose-Binding Lectin (MBL2) Genotyping in
Predicting the Risk of Recurrent
Otitis
Media (rOM)
Lieve
Nuytinck,
Els De Meester,
Martine
Van
Thielen,
and Paul Govaerts
1.
Introduction
. 281
2.
MBL2 Gene and Polymorphisms
. 283
3.
Materials and Methods
. 284
3.1.
Patients and Controls
. 284
3.2.
MBL2 Genotyping
. 285
4.
Results
. 285
5.
Discussion
. 286
6.
References
. 289
20.
Conformational Complexity of Complement Component C3
Bert J. C.
Janssen
and
Piet
Gros
1.
Introduction
. 291
2.
Structural Organization of C3
. 292
3.
Convertase Formation
. 296
4.
Decay Acceleration
. 299
5.
Cofactor Activity
. 301
6.
Signaling Roles of C3B Fragments
. 302
7.
Concluding Remarks
. 303
8.
Acknowledgments
. 304
9.
References
. 304
CONTENTS xv
21. Disease-Associated
Sequence Variations in Factor
H:
A Structural
Biology Approach
Andrew P. Herbert, Dinesh C.
Soares,
Michael
К.
Pangburn,
and Paul
N.
Barlow
1.
Introduction
. 313
2.
Regulation of the Complement System
. 314
3.
Factor
H
. 315
4.
Functional Sites of Factor
H
. 317
5.
Atypical Hemolytic
Uremie
Syndrome
. 318
6.
Age-Related
Macular
Degeneration
. 318
7.
Modeled Modules of Factor
H
. 319
8.
Predicted Structural Consequences of Amino-Acid Substitutions
. 321
9.
References
. 323
22. Transdermal
Pharmacology of Small Molecule Cyclic
C5a Antagonists
Lavinia M. Proctor, Trent M. Woodruff, Prakirti Sharma,
Ian A. Shiels, and Stephen M. Taylor
1.
Abstract
. 329
2.
Introduction
. 330
3.
Material and Methods
. 332
3.1.
Materials
. 332
3.2.
Isolation of Polymorphonuclear Leukocytes
. 332
3.3.
Receptor Binding Assay
. 333
3.4
Myeloperoxidase Release from PMNs
. 333
3.5.
In Vivo Studies
. 333
3.6.
Statistical Analysis
. 334
4.
Results
. 335
4.1.
In Vitro Activity of PMX Compounds
. 335
4.2. Transdermal
Pharmacokinetics of Cyclic C5a
Receptor Antagonists
. 335
4.3.
Effect of Administration of C5a Antagonists on
LPS-Induced Neutropenia and Hypotension
. 337
5.
Discussion
. 341
6.
References
. 342
23.
Inactivation of Complement by
Recombinant
Human
C3 Derivatives
Edzard
Spillner,
Johanna
Kölln,
and
Reinhard Bredehorst
1.
Introduction
. 347
2.
Generation of
CVF
Chimeras and C3 Derivatives
. 349
3.
Functional Characteristics of the C3 Derivatives
. 351
4.
The C345C Domain in Complement
. 353
5.
Therapeutical Implications
. 355
6.
Conclusions
. 356
7.
References
. 356
xvi CONTENTS
24.
Complement
Analysis in Clinic and Research
Tom E. Mollnes and Michael
Kirschfink
1.
Introduction
. 361
1.1.
The Complement System
. 361
2.
Clinical Indications for Complement Analysis
. 363
2.1.
Recurrent Infections
. 364
2.2.
Autoimmune Diseases
. 365
2.3.
Membranoproliferative Glomerulonephritis (MPGN)
and Hemolytic
Uremie
Syndrome
(HUS)
. 365
2.4.
Hereditary Angioedema
. 366
2.5.
Paroxysmal Nocturnal Hemoglobinuria (PNH)
. 366
3.
Complement Tests
. 366
3.1.
Functional Assays
. 366
3.2.
Protein Quantification of Individual Components
. 370
3.3.
Genetic Analysis
. 370
3.4.
Cell Surface Expression of Complement Proteins
. 370
3.5.
Analysis of Complement Activation Products
. 370
4.
Complement Analysis in Experimental Settings
. 372
4.1.
In Vitro Experiments with Human Serum and Blood
. 372
4.2.
Animal Experiments
. 373
5.
Outlook
. 375
6.
References
. 375
25.
Cell-Bound Complement Activation Products (CB-CAPs)
as a Source of Lupus
Biomarkers
Sarah J.
Calano,
Pei-an B. Shih, Chau-Ching Liu, Amy H.
Kao,
Jeannine
S. Navrátil,
Susan
Manzi,
and Joseph M. Ahearn
1.
Introduction
. 381
2.
Measurement of Complement in SLE
. 382
2.1.
Serum C3 and C4 and SLE Disease Activity
. 382
2.2.
Issues Associated with Measuring Soluble
.
Complement Components
. 382
2.3.
Complement Activation Products and SLE Disease Activity
. 384
3.
Cell-Bound Complement Activation Products
. 384
3.1.
Erythrocyte-Bound C4d as a Diagnostic Assay for SLE
. 385
3.2.
Reticulocyte-Bound C4d as an "Instant Messenger" of
Disease Activity in SLE
. 387
4.
Summary
. 387
5.
Acknowledgments
. 388
6.
References
. 388
Author Index
. 391
Subject Index
. 393 |
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| title | Current topics in complement |
| title_auth | Current topics in complement |
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| title_full | Current topics in complement [Aegean Conferences]. Ed. by John D. Lambris |
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| title_full_unstemmed | Current topics in complement [Aegean Conferences]. Ed. by John D. Lambris |
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