The impact for the clearance of dying cells of CRP: = Die Bedeutung des CRP für die Clearance sterbender Zellen
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
2012
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| Subjects: | |
| Online Access: | Volltext https://nbn-resolving.org/urn:nbn:de:bvb:29-opus-34522 http://d-nb.info/1025182707/34 Inhaltsverzeichnis |
| Physical Description: | 107 S. Ill., graph. Darst. |
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| 100 | 1 | |a Janko, Christina |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a The impact for the clearance of dying cells of CRP |b = Die Bedeutung des CRP für die Clearance sterbender Zellen |c von Christina Janko |
| 246 | 1 | 1 | |a Die Bedeutung des CRP für die Clearance sterbender Zellen |
| 264 | 1 | |c 2012 | |
| 300 | |a 107 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |a Erlangen-Nürnberg, Univ., Diss., 2012 | ||
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Record in the Search Index
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| adam_text | IMAGE 1
CONTENTS
1 SUMMARY 7
1 ZUSAMMENFASSUNG 9
2 INTRODUCTION 11
2.1 CRP 11
2.1.1 CRP IN THE ACUTE PHASE REACTION 11
2.1.2 PROTEIN STRUCTURE O F CRP 12
2.1.3 LIGANDSOFCRP 14
2.1.4 COMPLEMENT ACTIVATION BY CRP 15
2.1.5 INTERACTION WITH FCYR OF CRP 16
2.2 CELL DEATH AND CLEARANCE 17
2.2.1 APOPTOSIS AND NECROSIS 17
2.2.2 ANTI-INFLAMMATORY CLEARANCE OF APOPTOTIC CELLS 19
2.2.3 PRO-INFLAMMATORY CLEARANCE OF NECROTIC CELLS 21
2.3 SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) 24
2.3.1 CRP IN SLE 25
2.3.2 CRP AUTOANTIBODIES IN SLE 26
2.4 THE SCOPE OF THIS THESIS 27
3 MATERIALS & METHODS 28
3.1 MATERIALS 28
3.2 SLE AND APS STUDY GROUP 32
3.3 CYTOFLUOROMETRY AND MICROSCOPY 32
3.4 ISOLATION AND PREPARATION OF CRP FROM HUMAN SERUM 33
3.4.1 ISOLATION OF CRP FROM HUMAN SERUM 33
3.4.2 REMOVAL OF IGG CONTAMINATIONS 34
3.4.3 REMOVAL OF LPS CONTAMINATIONS 34
3.4.4 LABELLING OF CRP WITH FITC AND ALEXAFLUOR546 35
3.4.5 ASSESSMENT OF CRP PURITY 35
3.5 ISOLATION OF PMN AND PBMC FROM HUMAN WHOLE BLOOD 35
3.6 INDUCTION AND DETECTION OF CELL DEATH 36
3.6.1 INDUCTION OF CELL DEATH 36
3.6.2 MORPHOLOGY 36
3.6.3 AXV/PI STAINING 36
3.6.4 CRP/PI STAINING 37
HTTP://D-NB.INFO/1026544718
IMAGE 2
3.7 PRODUCTION OF SNEC 37
3.8 TREATMENT OF NECROTIC CELLS WITH DNASE-1 38
3.9 ANALYSES OF SUPERNATANTS FROM DYING AND DEAD CELLS 38
3.9.1 CRP INHIBITION ASSAY 38
3.9.2 INHIBITION OF THE RELEASE OF THE CRP ANTAGONIST 38
3.9.3 IDENTIFICATION OF THE CRP ANTAGONIST BY ENZYMATIC DIGESTION 39
3.9.4 IDENTIFICATION OF THE CRP ANTAGONIST BY MASS SPECTROMETRY 39
3. 10 PHAGOCYTOSIS ASSAY 40
3.10.1 PHAGOCYTOSIS OF AGED PMN OPSONISED WITH CRP +/- GPC 40
3.10.2 PHAGOCYTOSIS OF SNEC OPSONIZED WITH PATIENTS SERA 4 0
3.10.3 PHAGOCYTOSIS OF TERNARY COMPLEX FORMED BY SNEC, CRP, ANTI-CRP....
41
3.11 COMPLEMENT BINDING ASSAY 4 1
3.12 CYTOKINE ANALYSIS 4 1
3.13 ELISAS FOR DETECTION OF ANTIBODIES AGAINST CRP, GALECTINS AND
DSDNA... 42
3.14 LIGAND SPECIFIC INTERACTION EMPLOYING INERT PARTICLES 42
3.15 STATISTICAL ANALYSIS 43
4 RESULTS 44
4.1 ISOLATION OF CRP FROM HUMAN SERUM 4 4
4.2 OPSONISATION OF DYING AND DEAD CELLS BY CRP 45
4.2.1 BINDING OF CRP TO VIABLE, APOPTOTIC, AND NECROTIC CELLS 4 5
4.2.2 PRIMARY AND SECONDARY NECROTIC CELLS SHOW DIFFERENT BINDING
PATTERNS OF CRP . 48
4.2.3 APOPTOTIC CELLS RELEASE A CRP ANTAGONIST 49
4.2.4 RELEASE OF THE CRP ANTAGONIST IS DEPENDENT ON CASPASES AND PLA2..
50
4.2.5 THE CRP ANTAGONIST IS GLYCEROPHOSPHOCHOLINE 51
4.2.6 GPC DOES NOT INTERFERE WITH CRP DETECTION 54
4.2.7 GPC REDUCES CRP MEDIATED COMPLEMENT ACTIVATION 55
4.2.8 GPC DECREASES CRP MEDIATED PHAGOCYTOSIS 56
4.2.9 PBMC FROM A FEW PATIENTS WITH SLE SHOWED AN INCREASED GPC
RELEASE.. 57
4.3 CRP BINDING TO NUCLEAR TARGETS OF DYING AND DEAD CELLS 59
4.3.1 CRP BINDING IS INCREASED AFTER DNASE-1 TREATMENT 59
4.3.2 CRP BINDS TO CHROMATIN LOOSENED BY HYPOTONIC TREATMENT 61
4.3.3 CRP DOES NOT BIND NETS 62
4.4 CRP AUTOANTIBODIES IN SLE AND APS 63
IMAGE 3
4.4.1 SNEC EXPOSES BINDING SITES FOR SEVERAL OPSONINS 63
4.4.2 CRP BOUND TO SNEC IS ACCESSIBLE FOR EFFECTOR CELLS 64
4.4.3 ANTI-CRP AUTOANTIBODIES IN PATIENTS WITH SLE AND APS 65
4.4.4 ANTI-CRP ARE NOT ASSOCIATED WITH CRP, ANTI-DSDNA AND
ANTI-GALECTIN-8 IN SLE 6 6
4.4.5 OPSONISATION OF SNEC FOSTERS THEIR PHAGOCYTOSIS BY MACROPHAGES AND
INDUCES AN INFLAMMATORY CYTOKINE RESPONSE 68
4.4.6 SNEC, CRP, AND ANTI-CRP AUTOANTIBODIES FORM TERNARY COMPLEXES
SHIFTING THE CLEARANCE TOWARDS INFLAMMATION 69
5 DISCUSSION 71
5.1 CRP BINDING TO DYING AND DEAD CELLS 71
5.1.1 CRP BINDS TO APOPTOTIC PMN BUT NOT TO APOPTOTIC PBMC 71
5.1.2 DNASE-1 TREATMENT FOSTERS CRP BINDING TO NECROTIC CELLS 72
5.1.3 DURING APOPTOSIS THE CRP TARGET LPC IS CLEAVED AND RELEASED AS
GPC74
5.1.4 IMPLICATIONS OF THE GPC RELEASE FOR THE CRP MEDIATED CLEARANCE 76
5.2 ANTI-CRP AUTOANTIBODIES 77
5.2.1 OCCURRENCE OF ANTI-CRP AUTOANTIBODIES 77
5.2.2 ANTI-CRP ANTIBODIES SHIFT THE CLEARANCE TOWARDS INFLAMMATION 79
5.3 CONCLUSIONS 82
6 REFERENCES 83
7 ABBREVIATION INDEX 97
8 FIGURE INDEX 100
PUBLICATIONS AND PRESENTATIONS 102
|
| any_adam_object | 1 |
| author | Janko, Christina |
| author_facet | Janko, Christina |
| author_role | aut |
| author_sort | Janko, Christina |
| author_variant | c j cj |
| building | Verbundindex |
| bvnumber | BV040451237 |
| collection | ebook |
| ctrlnum | (OCoLC)815941047 (DE-599)DNB1025182707 |
| dewey-full | 571.936 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 571 - Physiology & related subjects |
| dewey-raw | 571.936 |
| dewey-search | 571.936 |
| dewey-sort | 3571.936 |
| dewey-tens | 570 - Biology |
| discipline | Biologie |
| format | Thesis Book |
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| spelling | Janko, Christina Verfasser aut The impact for the clearance of dying cells of CRP = Die Bedeutung des CRP für die Clearance sterbender Zellen von Christina Janko Die Bedeutung des CRP für die Clearance sterbender Zellen 2012 107 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Erlangen-Nürnberg, Univ., Diss., 2012 Nekrose (DE-588)4171420-9 gnd rswk-swf Apoptosis (DE-588)4291096-1 gnd rswk-swf Clearance (DE-588)4148067-3 gnd rswk-swf Opsonisierung (DE-588)7546602-8 gnd rswk-swf Autoimmunität (DE-588)4319435-7 gnd rswk-swf C-reaktives Protein (DE-588)4226338-4 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content C-reaktives Protein (DE-588)4226338-4 s Apoptosis (DE-588)4291096-1 s Nekrose (DE-588)4171420-9 s Opsonisierung (DE-588)7546602-8 s Clearance (DE-588)4148067-3 s Autoimmunität (DE-588)4319435-7 s DE-604 Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:29-opus-34522 https://open.fau.de/handle/openfau/2322 Verlag kostenfrei Volltext https://nbn-resolving.org/urn:nbn:de:bvb:29-opus-34522 Resolving-System http://d-nb.info/1025182707/34 Langzeitarchivierung Nationalbibliothek DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025298887&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Janko, Christina The impact for the clearance of dying cells of CRP = Die Bedeutung des CRP für die Clearance sterbender Zellen Nekrose (DE-588)4171420-9 gnd Apoptosis (DE-588)4291096-1 gnd Clearance (DE-588)4148067-3 gnd Opsonisierung (DE-588)7546602-8 gnd Autoimmunität (DE-588)4319435-7 gnd C-reaktives Protein (DE-588)4226338-4 gnd |
| subject_GND | (DE-588)4171420-9 (DE-588)4291096-1 (DE-588)4148067-3 (DE-588)7546602-8 (DE-588)4319435-7 (DE-588)4226338-4 (DE-588)4113937-9 |
| title | The impact for the clearance of dying cells of CRP = Die Bedeutung des CRP für die Clearance sterbender Zellen |
| title_alt | Die Bedeutung des CRP für die Clearance sterbender Zellen |
| title_auth | The impact for the clearance of dying cells of CRP = Die Bedeutung des CRP für die Clearance sterbender Zellen |
| title_exact_search | The impact for the clearance of dying cells of CRP = Die Bedeutung des CRP für die Clearance sterbender Zellen |
| title_full | The impact for the clearance of dying cells of CRP = Die Bedeutung des CRP für die Clearance sterbender Zellen von Christina Janko |
| title_fullStr | The impact for the clearance of dying cells of CRP = Die Bedeutung des CRP für die Clearance sterbender Zellen von Christina Janko |
| title_full_unstemmed | The impact for the clearance of dying cells of CRP = Die Bedeutung des CRP für die Clearance sterbender Zellen von Christina Janko |
| title_short | The impact for the clearance of dying cells of CRP |
| title_sort | the impact for the clearance of dying cells of crp die bedeutung des crp fur die clearance sterbender zellen |
| title_sub | = Die Bedeutung des CRP für die Clearance sterbender Zellen |
| topic | Nekrose (DE-588)4171420-9 gnd Apoptosis (DE-588)4291096-1 gnd Clearance (DE-588)4148067-3 gnd Opsonisierung (DE-588)7546602-8 gnd Autoimmunität (DE-588)4319435-7 gnd C-reaktives Protein (DE-588)4226338-4 gnd |
| topic_facet | Nekrose Apoptosis Clearance Opsonisierung Autoimmunität C-reaktives Protein Hochschulschrift |
| url | https://open.fau.de/handle/openfau/2322 https://nbn-resolving.org/urn:nbn:de:bvb:29-opus-34522 http://d-nb.info/1025182707/34 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025298887&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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