The role of nucleic acid sensing in a new established model of pulmonary vasculitis:
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
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Bonn
2020
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Internformat
MARC
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| 016 | 7 | |a 1223034992 |2 DE-101 | |
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| 100 | 1 | |a Viehmann, Susanne Friederike |e Verfasser |0 (DE-588)1220523755 |4 aut | |
| 245 | 1 | 0 | |a The role of nucleic acid sensing in a new established model of pulmonary vasculitis |c Susanne Friederike Viehmann aus Essen |
| 264 | 1 | |a Bonn |c 2020 | |
| 300 | |a 116 Seiten |b Illustrationen |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Rheinische Friedrich-Wilhelms-Universität Bonn |d 2020 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m B:DE-101 |q application/pdf |u https://d-nb.info/1223034992/04 |3 Inhaltsverzeichnis |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032618535&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-032618535 | ||
Datensatz im Suchindex
| _version_ | 1804182330062929921 |
|---|---|
| adam_text | CONTENT
LIST
OF
ABBREVIATIONS
7
1
INTRODUCTION
9
1.1.
SYSTEMIC
VASCULITIDES
9
1.2.
ANCA-ASSOCIATED
VASCULITIS
10
1.3.
TREATMENT
OF
ANCA-ASSOCIATED
VASCULITIS
11
1.4.
PATHOGENESIS
OF
ANCA-ASSOCIATED
VASCULITIS
11
1.5.
MECHANISMS
OF
ANCA
PRODUCTION
AND
PATHOGENICITY
OF
ANCA
14
1.6.
CELLULAR
AND
HUMORAL
INVOLVEMENT
IN
ANCA-ASSOCIATED
VASCULITIS
16
1.7.
NUCLEIC
ACID
RECOGNITION
IN
INNATE
IMMUNITY
18
1.7.1.
THE
CGAS-STING
PATHWAY
OF
NUCLEIC
ACID
RECOGNITION
20
1.7.2.
CGAS-STING
MEDIATED
AUTOIMMUNITY
21
1.8.
EXPERIMENTAL
MOUSE
MODELS
OF
ANCA-ASSOCIATED
VASCULITIS
22
1.8.1.
PASSIVE
IMMUNIZATION
MODELS
22
1.8.2.
ACTIVE
IMMUNIZATION
MODELS
23
1.8.3.
FUTURE
DIRECTIONS
FOR
ANIMAL
MODELS
OF
ANCA-ASSOCIATED
VASCULITIS
24
1.9.
AIM
OF
THE
PROJECT
25
2
MATERIAL
AND
METHODS
26
2.1.
MATERIAL
26
2.1.1.
TECHNICAL
EQUIPMENT
26
2.1.2.
CONSUMABLES
28
2.1.3.
CHEMICALS
AND
REAGENTS
30
2.1.4.
MEDIA,
SERA
AND
BUFFER
32
2.1.5.
ANTIBODIES
AND
INHIBITORS
32
2.1.5.1.
PURIFIED
ANTIBODIES
FOR
IN
VIVO
USE
32
2.1.5.2.
ANTIBODIES
FOR
FLOW
CYTOMETRY
33
2.1.5.3.
ANTIBODIES
FOR
HISTOLOGY
34
2.1.5.4.
SMALL
MOLECULE
INHIBITORS
34
2.1.6.
SOFTWARE
35
2.1.7.
ILLUSTRATIONS
35
2.1.8.
MOUSE
STRAINS
36
2.2.
METHODS
38
4
2.2.1.
AUTOIMMUNE
MPO-ANCA
PULMONARY
MODEL
38
2.2.2.
MONITORING
WEIGHT
LOSS
AND
PULSE
OXIMETRY
38
2.2.3.
ASSESSMENT
OF
PULMONARY
DISEASE
39
2.2.4.
COLLECTION
OF
BALF,
BLOOD
AND
LUNGS
39
2.2.5.
QUANTIFICATION
OF
PULMONARY
HEMORRHAGES
40
2.2.6.
FLOW
CYTOMETRY
OF
BALF
AND
BLOOD
40
2.2.7.
QUANTIFICATION
OF
ROS
IN
BALF
AND
BLOOD
42
2.2.8.
UNIFORM
MANIFOLD
APPROXIMATION
AND
PROJECTION
FOR
DIMENSION
REDUCTION
(UMAP)
42
2.2.9.
QUANTIFICATION
OF
FREE
EXTRACELLULAR
DNA
IN
BALF
42
2.2.10.
QUANTIFICATION
OF
CGAMP
IN
BALF
43
2.2.11.
HISTOLOGY
43
2.2.12.
LIGHT
SHEET
MICROSCOPY
(LSM)
46
2.2.13.
IMAGE
PROCESSING
AND
DISPLAY
FOR
LSM
46
2.2.14.
CONFOCAL
MICROSCOPY
OF
LUNG
46
2.2.15.
GENE
EXPRESSION
ANALYSIS
47
2.2.16.
PHARMACOLOGICAL
INHIBITION
OF
IFNAR-I
AND
STING
49
2.2.17.
QUANTIFICATION
AND
STATISTICAL
ANALYSES
49
3
RESULTS
50
3.1.
ESTABLISHMENT
OF
A
NEW
MODEL
FOR
AUTOIMMUNE
PULMONARY
VASCULITIS
IN
B6
MICE
50
3.1.1.
I.T.
APPLICATION
OF
FMLP
AND
LPS
PROMOTES
AN
INCREASE
OF
NEUTROPHILS
IN
BLOOD
AND
BALF
OF
B6
MICE
50
3.1.2.
FMLP
AND
LPS
AGGRAVATE
THE
PRODUCTION
OF
ROS
BY
NEUTROPHILS
IN
BLOOD
AND
BALF
OF
B6
MICE
52
3.1.3.
COMBINATORIAL
ADMINISTRATION
OF
BACTERIAL
LIGANDS
AND
A-MPO
IGG
IS
REQUIRED
TO
INDUCE
ANCA-ASSOCIATED
PULMONARY
VASCULITIS
IN
B6
MICE
53
3.1.4.
COMBINATORIAL
ADMINISTRATION
OF
FMLP,
LPS
AND
A-MPO
IS
ASSOCIATED
WITH
ABROGATED
BLOOD
VESSEL
INTEGRITY
IN
THE
LUNG
55
3.1.5.
AAV
TREATMENT
ENHANCES
IMMUNE
CELL
INFILTRATION
AND
PATHOLOGY
IN
LUNG
TISSUE
57
5
3.1.6.
A-MPO
ENHANCES
FMLP
AND
LPS
INDUCED
IMMUNE
CELL
RECRUITMENT
IN
THE
BALF
60
3.2.
DNA-MEDIATED
TYPE
I
IFN
RESPONSES
PROMOTE
CONGENIC
INTERFERONOPATHIES
63
3.2.1.
ABSENCE
OF
CGAS
DOES
NOT
INFLUENCE
INDUCTION
OF
PULMONARY
AAV
IN
VIVO.
64
3.2.2.
PATHOLOGIC
DISEASE
PHENOTYPE
OF
A-MPO
INDUCED
ANCA-ASSOCIATED
PULMONARY
VASCULITIS
IS
ABROGATED
IN
STING
7
*
MICE
66
3.3.
DOWNSTREAM
MOLECULES
OF
CGAS-STING
ARE
CRITICAL
MEDIATORS
FOR
AAV
INDUCED
PULMONARY VASCULITIS
69
3.3.1.
ISGS
ARE
UPREGULATED
IN
AAV-TREATED
WT
AND
STING
*
7
*
MICE
69
3.3.2.
TYPE-I
IFN
IS
REQUIRED
FOR
THE
DEVELOPMENT
OF
SEVERE
PULMONARY
VASCULITIS
72
3.3.3.
TNFA
7
*
AND
STAT6
MEDIATE
DISEASE
PROGRESSION
IN
PULMONARY
VASCULITIS
74
3.3.4.
THE
NLRP3
INFLAMMASOME
IS
NOT
INVOLVED
IN
DISEASE
PROGRESSION
OF
A-MPO
INDUCED
PULMONARY
VASCULITIS
78
3.4.
PHARMACOLOGICAL
INHIBITION
OF
STING
IMPROVES
OUTCOME
OF
A-MPO
INDUCED
ANCA-ASSOCIATED
PULMONARY
VASCULITIS
82
3.5.
PULMONARY
AAV
INDUCES
CASPASE-INDEPENDENT
DEATH
OF
ENDOTHELIAL
CELLS
IN
MOUSE
LUNGS
84
4
DISCUSSION
87
4.1.
BACTERIAL
LIGANDS
AND
ANCA
PROVOKE
AUTOIMMUNE
PULMONARY VASCULITIS
87
4.2.
STING
ACTIVATION
PROMOTES
IFN-I
DEPENDENT
AUTOIMMUNE
PULMONARY
VASCULITIS
90
4.3.
PHARMACOLOGICAL
INHIBITION
OF
THE
STING/IFNAR
PATHWAY
AMELIORATES
AUTOIMMUNE
PULMONARY
VASCULITIS
94
4.4.
AUTOIMMUNE
PULMONARY
VASCULITIS
TRIGGERS
STING-DEPENDENT
DEATH
OF
ENDOTHELIAL
CELLS
IN
THE
LUNG
95
5
SUMMARY
96
6
LIST
OF
FIGURES
98
7
LIST
OF
TABLES
99
8
REFERENCES
100
9
ACKNOWLEDGEMENT
116
|
| adam_txt |
CONTENT
LIST
OF
ABBREVIATIONS
7
1
INTRODUCTION
9
1.1.
SYSTEMIC
VASCULITIDES
9
1.2.
ANCA-ASSOCIATED
VASCULITIS
10
1.3.
TREATMENT
OF
ANCA-ASSOCIATED
VASCULITIS
11
1.4.
PATHOGENESIS
OF
ANCA-ASSOCIATED
VASCULITIS
11
1.5.
MECHANISMS
OF
ANCA
PRODUCTION
AND
PATHOGENICITY
OF
ANCA
14
1.6.
CELLULAR
AND
HUMORAL
INVOLVEMENT
IN
ANCA-ASSOCIATED
VASCULITIS
16
1.7.
NUCLEIC
ACID
RECOGNITION
IN
INNATE
IMMUNITY
18
1.7.1.
THE
CGAS-STING
PATHWAY
OF
NUCLEIC
ACID
RECOGNITION
20
1.7.2.
CGAS-STING
MEDIATED
AUTOIMMUNITY
21
1.8.
EXPERIMENTAL
MOUSE
MODELS
OF
ANCA-ASSOCIATED
VASCULITIS
22
1.8.1.
PASSIVE
IMMUNIZATION
MODELS
22
1.8.2.
ACTIVE
IMMUNIZATION
MODELS
23
1.8.3.
FUTURE
DIRECTIONS
FOR
ANIMAL
MODELS
OF
ANCA-ASSOCIATED
VASCULITIS
24
1.9.
AIM
OF
THE
PROJECT
25
2
MATERIAL
AND
METHODS
26
2.1.
MATERIAL
26
2.1.1.
TECHNICAL
EQUIPMENT
26
2.1.2.
CONSUMABLES
28
2.1.3.
CHEMICALS
AND
REAGENTS
30
2.1.4.
MEDIA,
SERA
AND
BUFFER
32
2.1.5.
ANTIBODIES
AND
INHIBITORS
32
2.1.5.1.
PURIFIED
ANTIBODIES
FOR
IN
VIVO
USE
32
2.1.5.2.
ANTIBODIES
FOR
FLOW
CYTOMETRY
33
2.1.5.3.
ANTIBODIES
FOR
HISTOLOGY
34
2.1.5.4.
SMALL
MOLECULE
INHIBITORS
34
2.1.6.
SOFTWARE
35
2.1.7.
ILLUSTRATIONS
35
2.1.8.
MOUSE
STRAINS
36
2.2.
METHODS
38
4
2.2.1.
AUTOIMMUNE
MPO-ANCA
PULMONARY
MODEL
38
2.2.2.
MONITORING
WEIGHT
LOSS
AND
PULSE
OXIMETRY
38
2.2.3.
ASSESSMENT
OF
PULMONARY
DISEASE
39
2.2.4.
COLLECTION
OF
BALF,
BLOOD
AND
LUNGS
39
2.2.5.
QUANTIFICATION
OF
PULMONARY
HEMORRHAGES
40
2.2.6.
FLOW
CYTOMETRY
OF
BALF
AND
BLOOD
40
2.2.7.
QUANTIFICATION
OF
ROS
IN
BALF
AND
BLOOD
42
2.2.8.
UNIFORM
MANIFOLD
APPROXIMATION
AND
PROJECTION
FOR
DIMENSION
REDUCTION
(UMAP)
42
2.2.9.
QUANTIFICATION
OF
FREE
EXTRACELLULAR
DNA
IN
BALF
42
2.2.10.
QUANTIFICATION
OF
CGAMP
IN
BALF
43
2.2.11.
HISTOLOGY
43
2.2.12.
LIGHT
SHEET
MICROSCOPY
(LSM)
46
2.2.13.
IMAGE
PROCESSING
AND
DISPLAY
FOR
LSM
46
2.2.14.
CONFOCAL
MICROSCOPY
OF
LUNG
46
2.2.15.
GENE
EXPRESSION
ANALYSIS
47
2.2.16.
PHARMACOLOGICAL
INHIBITION
OF
IFNAR-I
AND
STING
49
2.2.17.
QUANTIFICATION
AND
STATISTICAL
ANALYSES
49
3
RESULTS
50
3.1.
ESTABLISHMENT
OF
A
NEW
MODEL
FOR
AUTOIMMUNE
PULMONARY
VASCULITIS
IN
B6
MICE
50
3.1.1.
I.T.
APPLICATION
OF
FMLP
AND
LPS
PROMOTES
AN
INCREASE
OF
NEUTROPHILS
IN
BLOOD
AND
BALF
OF
B6
MICE
50
3.1.2.
FMLP
AND
LPS
AGGRAVATE
THE
PRODUCTION
OF
ROS
BY
NEUTROPHILS
IN
BLOOD
AND
BALF
OF
B6
MICE
52
3.1.3.
COMBINATORIAL
ADMINISTRATION
OF
BACTERIAL
LIGANDS
AND
A-MPO
IGG
IS
REQUIRED
TO
INDUCE
ANCA-ASSOCIATED
PULMONARY
VASCULITIS
IN
B6
MICE
53
3.1.4.
COMBINATORIAL
ADMINISTRATION
OF
FMLP,
LPS
AND
A-MPO
IS
ASSOCIATED
WITH
ABROGATED
BLOOD
VESSEL
INTEGRITY
IN
THE
LUNG
55
3.1.5.
AAV
TREATMENT
ENHANCES
IMMUNE
CELL
INFILTRATION
AND
PATHOLOGY
IN
LUNG
TISSUE
57
5
3.1.6.
A-MPO
ENHANCES
FMLP
AND
LPS
INDUCED
IMMUNE
CELL
RECRUITMENT
IN
THE
BALF
60
3.2.
DNA-MEDIATED
TYPE
I
IFN
RESPONSES
PROMOTE
CONGENIC
INTERFERONOPATHIES
63
3.2.1.
ABSENCE
OF
CGAS
DOES
NOT
INFLUENCE
INDUCTION
OF
PULMONARY
AAV
IN
VIVO.
64
3.2.2.
PATHOLOGIC
DISEASE
PHENOTYPE
OF
A-MPO
INDUCED
ANCA-ASSOCIATED
PULMONARY
VASCULITIS
IS
ABROGATED
IN
STING
7
*
MICE
66
3.3.
DOWNSTREAM
MOLECULES
OF
CGAS-STING
ARE
CRITICAL
MEDIATORS
FOR
AAV
INDUCED
PULMONARY VASCULITIS
69
3.3.1.
ISGS
ARE
UPREGULATED
IN
AAV-TREATED
WT
AND
STING
*
7
*
MICE
69
3.3.2.
TYPE-I
IFN
IS
REQUIRED
FOR
THE
DEVELOPMENT
OF
SEVERE
PULMONARY
VASCULITIS
72
3.3.3.
TNFA
7
*
AND
STAT6
MEDIATE
DISEASE
PROGRESSION
IN
PULMONARY
VASCULITIS
74
3.3.4.
THE
NLRP3
INFLAMMASOME
IS
NOT
INVOLVED
IN
DISEASE
PROGRESSION
OF
A-MPO
INDUCED
PULMONARY
VASCULITIS
78
3.4.
PHARMACOLOGICAL
INHIBITION
OF
STING
IMPROVES
OUTCOME
OF
A-MPO
INDUCED
ANCA-ASSOCIATED
PULMONARY
VASCULITIS
82
3.5.
PULMONARY
AAV
INDUCES
CASPASE-INDEPENDENT
DEATH
OF
ENDOTHELIAL
CELLS
IN
MOUSE
LUNGS
84
4
DISCUSSION
87
4.1.
BACTERIAL
LIGANDS
AND
ANCA
PROVOKE
AUTOIMMUNE
PULMONARY VASCULITIS
87
4.2.
STING
ACTIVATION
PROMOTES
IFN-I
DEPENDENT
AUTOIMMUNE
PULMONARY
VASCULITIS
90
4.3.
PHARMACOLOGICAL
INHIBITION
OF
THE
STING/IFNAR
PATHWAY
AMELIORATES
AUTOIMMUNE
PULMONARY
VASCULITIS
94
4.4.
AUTOIMMUNE
PULMONARY
VASCULITIS
TRIGGERS
STING-DEPENDENT
DEATH
OF
ENDOTHELIAL
CELLS
IN
THE
LUNG
95
5
SUMMARY
96
6
LIST
OF
FIGURES
98
7
LIST
OF
TABLES
99
8
REFERENCES
100
9
ACKNOWLEDGEMENT
116 |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| author | Viehmann, Susanne Friederike |
| author_GND | (DE-588)1220523755 |
| author_facet | Viehmann, Susanne Friederike |
| author_role | aut |
| author_sort | Viehmann, Susanne Friederike |
| author_variant | s f v sf sfv |
| building | Verbundindex |
| bvnumber | BV047213781 |
| ctrlnum | (OCoLC)1236019550 (DE-599)DNB1223034992 |
| discipline | Medizin |
| discipline_str_mv | Medizin |
| format | Thesis Book |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV047213781 |
| illustrated | Illustrated |
| index_date | 2024-07-03T16:55:13Z |
| indexdate | 2024-07-10T09:05:50Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-032618535 |
| oclc_num | 1236019550 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | 116 Seiten Illustrationen 30 cm |
| publishDate | 2020 |
| publishDateSearch | 2020 |
| publishDateSort | 2020 |
| record_format | marc |
| spelling | Viehmann, Susanne Friederike Verfasser (DE-588)1220523755 aut The role of nucleic acid sensing in a new established model of pulmonary vasculitis Susanne Friederike Viehmann aus Essen Bonn 2020 116 Seiten Illustrationen 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Rheinische Friedrich-Wilhelms-Universität Bonn 2020 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1223034992/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032618535&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Viehmann, Susanne Friederike The role of nucleic acid sensing in a new established model of pulmonary vasculitis |
| subject_GND | (DE-588)4113937-9 |
| title | The role of nucleic acid sensing in a new established model of pulmonary vasculitis |
| title_auth | The role of nucleic acid sensing in a new established model of pulmonary vasculitis |
| title_exact_search | The role of nucleic acid sensing in a new established model of pulmonary vasculitis |
| title_exact_search_txtP | The role of nucleic acid sensing in a new established model of pulmonary vasculitis |
| title_full | The role of nucleic acid sensing in a new established model of pulmonary vasculitis Susanne Friederike Viehmann aus Essen |
| title_fullStr | The role of nucleic acid sensing in a new established model of pulmonary vasculitis Susanne Friederike Viehmann aus Essen |
| title_full_unstemmed | The role of nucleic acid sensing in a new established model of pulmonary vasculitis Susanne Friederike Viehmann aus Essen |
| title_short | The role of nucleic acid sensing in a new established model of pulmonary vasculitis |
| title_sort | the role of nucleic acid sensing in a new established model of pulmonary vasculitis |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1223034992/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032618535&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT viehmannsusannefriederike theroleofnucleicacidsensinginanewestablishedmodelofpulmonaryvasculitis |
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