The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice:
Gespeichert in:
| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2011
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| Schlagworte: | |
| Online-Zugang: | Volltext Inhaltsverzeichnis |
| Beschreibung: | Online erschienen: 2013 |
| Beschreibung: | VII, 110 Bl. Ill., graph. Darst. |
Internformat
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| 245 | 1 | 0 | |a The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice |c von Frauke May |
| 246 | 1 | 3 | |a Die Rolle der (hem)ITAM-gekoppelten Rezeptoren C-type lectin-like receptor 2 (CLEC-2) und Glykoprotein (GP) VI in der Thrombozytenfunktion: in vitro- und in vivo-Studien in Mäusen |
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Datensatz im Suchindex
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|---|---|
| adam_text | IMAGE 1
TABLE OF CONTENTS
TABLE OF CONTENTS
1 INTRODUCTION 1
1.1 PLATELET ACTIVATION AND THROMBUS FORMATION 1
1.2 SIGNALING EVENTS IN THE PROCESS OF PLATELET ACTIVATION 3
1.3 THE C-TYPE LECTIN-LIKE RECEPTOR 2 (CLEC-2) 5
1.3.1 CHROMOSOMAL LOCATION, EXPRESSION PROFILE AND PROTEIN STRUCTURE OF
CLEC-2 5
1.3.2 CLEC-2-INDUCED INTRACELLULAR SIGNALING 7
1.3.3 EXTRACELLULAR LIGANDS AND PHYSIOLOGICAL FUNCTIONS OF CLEC-2 9
1.3.4 THE ROLE OF CLEC-2 IN HEMOSTASIS AND THROMBOSIS 11
1.4 THE MAJOR COLLAGEN RECEPTOR GLYCOPROTEIN (GP) VI 12
1.4.1 SIGNAL TRANSDUCTION OF GPVI 12
1.4.2 DOWN-REGULATION OF GPVI ON THE PLATELET SURFACE USING MONOCLONAL
ANTIBODIES.... 13
1.5 COMPARISON OF SIGNAL TRANSDUCTION PATHWAYS OF GPVI AND CLEC-2 16
1.6 IMMUNODEPLETION OF PLATELET SURFACE RECEPTORS AS A NOVEL STRATEGY
FOR ANTI-THROMBOTIC
THERAPY 17
1.7 AIM OF THE STUDY 18
2 MATERIALS AND METHODS 19
2.1 MATERIALS 19
2.1.1 KITS AND CHEMICALS 19
2.1.2 CELL CULTURE MATERIALS 21
2.1.3 ANTIBODIES 22
2.1.4 ANIMALS 22
2.1.5 CELL LINES 23
2.1.6 BUFFERS AND MEDIA 23
2.2 METHODS 28
2.2.1 HUMAN EMBRYONIC KIDNEY (HEK) 293 CELL CULTURE 28
2.2.2 PRODUCTION OF MONOCLONAL ANTIBODIES 29
2.2.3 MODIFICATION OF ANTIBODIES 31
2.2.4 MOUSE TREATMENT WITH ANTIBODIES 33
2.2.5 MOUSE GENOTYPING USING FLOW CYTOMETRY 33
HTTP://D-NB.INFO/1041809735
IMAGE 2
TABLE OF CONTENTS
2.2.6 IMMUNOPRECIPITATION AND IMMUNOBLOTTING 33
2.2.7 IN VITRO ANALYSIS OF PLATELET FUNCTION 34
2.2.8 IN VIVO ANALYSIS OF PLATELET FUNCTION 37
2.2.9 HISTOLOGY 39
2.2.10 DATA ANALYSIS 39
3 RESULTS 40
3.1 CHARACTERIZATION OF THE ANTI-MOUSE CLEC-2 ANTIBODY INU1 40
3.1.1 GENERATION OF THE MONOCLONAL ANTI-MOUSE CLEC-2 ANTIBODY, INU1 40
3.1.2 INU1 RECOGNIZES MOUSE CLEC-2 ON PLATELETS 42
3.1.3 INU1-ALEXA488 IS SUITABLE FOR IMMUNO-FLUORESCENT STAININGS ON
PLATELETS 44
3.1.4 ANALYSIS OF CLEC-2 EXPRESSION ON IMMUNE CELLS 45
3.1.5 FAB-FRAGMENTS OF INU1 PARTIALLY INHIBIT CLEC-2 FUNCTION IN VITRO
47
3.1.6 INU1-LGG INDUCES THE LOSS OF CLEC-2 IN CIRCULATING PLATELETS IN
VIVO 48
3.1.7 CLEC-2-DEFICIENT PLATELETS SHOW AN ABOLISHED RESPONSE TO
RHODOCYTIN BUT NORMAL
RESPONSES TO CLASSIC AGONISTS 51
3.1.8 CLEC-2 IS REQUIRED FOR STABLE THROMBUS FORMATION UNDER FLOW 53
3.1.9 INCREASED TAIL BLEEDING TIMES IN CLEC-2-DEFICIENT MICE 57
3.1.10 CLEC-2-DEFICIENT MICE IN MODELS OF ARTERIAL THROMBOSIS AND
ISCHEMIC STROKE 57
3.1.11 INU1-FAB-FRAGMENT-INDUCED LETHALITY IN MICE 61
3.2 GENERATION OF THE SECOND ANTI-MURINE CLEC-2 ANTIBODY INU2 64
3.3 ABOLISHED ARTERIAL THROMBUS FORMATION AND SEVERELY DEFECTIVE
HEMOSTASIS IN
GPVI/CLEC-2 DOUBLE-DEFICIENT MICE 66
3.3.1 INDEPENDENT ANTIBODY-MEDIATED DOWN-REGULATION OF GPVI AND CLEC-2
IN PLATELETS
IN VIVO 66
3.3.2 IN VITRO ANALYSIS OF PLATELET FUNCTION UPON ANTIBODY-INDUCED GPVI
AND CLEC-2
DOUBLE-DEFICIENCY 67
3.3.3 IN VIVO ANALYSIS OF ANTIBODY-INDUCED GPVI AND CLEC-2
DOUBLE-DEFICIENCY IN MICE..
72
3.3.4 ANALYSIS OF GP6^/CLEC-2-DEFICIENT MICE 75
4 DISCUSSION 79
4.1 CHALLENGES DURING THE GENERATION OF ANTI-MOUSE CLEC-2 ANTIBODIES 79
IMAGE 3
TABLE OF CONTENTS
4.2 THE PLATELET ACTIVATING RECEPTOR CLEC-2 IS ESSENTIAL IN THE PROCESS
OF THROMBUS
FORMATION 80
4.2.1 TREATMENT WITH INU1 LEADS TO DOWN-REGULATION OF CLEC-2 IN VIVO 80
4.2.2 THROMBUS INSTABILITY IN CLEC-2-DEPIETED MICE 82
4.3 CLEC-2 EXPRESSION ON IMMUNE CELLS 86
4.4 INU1-FAB-FRAGMENT-INDUCED LETHALITY IN MICE 88
4.5 POTENTIAL SIDE EFFECTS OF INU1-LGG TREATMENT 89
4.6 GPVI AND CLEC-2 PLAY REDUNDANT ROLES IN HEMOSTASIS AND THROMBOSIS 90
4.7 CLEC-2 AS A NOVEL THERAPEUTIC TARGET 92
4.8 CONCLUDING REMARKS AND FUTURE PLANS 93
5 REFERENCES 94
6 APPENDIX 103
|
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| spelling | May, Frauke 1981- Verfasser (DE-588)1037261704 aut The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice von Frauke May Die Rolle der (hem)ITAM-gekoppelten Rezeptoren C-type lectin-like receptor 2 (CLEC-2) und Glykoprotein (GP) VI in der Thrombozytenfunktion: in vitro- und in vivo-Studien in Mäusen 2011 VII, 110 Bl. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Online erschienen: 2013 Würzburg, Univ., Diss., 2011 Thrombose (DE-588)4059963-2 gnd rswk-swf Rezeptor (DE-588)4049722-7 gnd rswk-swf Thrombozyt (DE-588)4059964-4 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Thrombozyt (DE-588)4059964-4 s Rezeptor (DE-588)4049722-7 s Thrombose (DE-588)4059963-2 s DE-604 Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:20-opus-65383 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-65383 Resolving-System kostenfrei Volltext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026131174&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | May, Frauke 1981- The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice Thrombose (DE-588)4059963-2 gnd Rezeptor (DE-588)4049722-7 gnd Thrombozyt (DE-588)4059964-4 gnd |
| subject_GND | (DE-588)4059963-2 (DE-588)4049722-7 (DE-588)4059964-4 (DE-588)4113937-9 |
| title | The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice |
| title_alt | Die Rolle der (hem)ITAM-gekoppelten Rezeptoren C-type lectin-like receptor 2 (CLEC-2) und Glykoprotein (GP) VI in der Thrombozytenfunktion: in vitro- und in vivo-Studien in Mäusen |
| title_auth | The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice |
| title_exact_search | The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice |
| title_full | The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice von Frauke May |
| title_fullStr | The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice von Frauke May |
| title_full_unstemmed | The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice von Frauke May |
| title_short | The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice |
| title_sort | the role of the hem itam coupled receptors c type lectin like receptor 2 clec 2 and glycoprotein gp vi for platelet function in vitro and in vivo studies in mice |
| topic | Thrombose (DE-588)4059963-2 gnd Rezeptor (DE-588)4049722-7 gnd Thrombozyt (DE-588)4059964-4 gnd |
| topic_facet | Thrombose Rezeptor Thrombozyt Hochschulschrift |
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