A PLCγ2-independent platelet collagen aggregation requiring functional association of GPVI and integrin α2β1

被引:36
作者
Mangin, P
Nonne, C
Eckly, A
Ohlmann, P
Freund, M
Nieswandt, B
Cazenave, JP
Gachet, C
Lanza, F
机构
[1] INSERM, U 311, Etablissement Francais Sang Alsace, F-69065 Strasbourg, France
[2] Univ Wurzburg, Rudolf Virchow Ctr Expt Biomed, Wurzburg, Germany
关键词
collagen; integrin alpha(2)beta(1); phospholipase c-gamma 2; knockout mouse; platelet; signal transduction;
D O I
10.1016/S0014-5793(03)00337-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The role of the phospholipase C (PLC)gamma2 isotype in platelet activation was evaluated by studying PLCgamma2 -/- mice. These mice have a prolonged bleeding time but their platelets respond normally to non-collagenous agonists. PLCgamma2-null platelets show residual aggregation response to collagen fibres (6% versus 74% for wild-type) with minimal granule secretion and no shape change. A delayed shape change is observed at later aggregation times. Specific activation by glycoprotein (GP)VI agonists (convulxin, collagen-related peptide and GPVI crosslinking) is, however, abolished. Antibodies against integrin alpha(2)beta(1) and GPVI each inhibit the residual collagen response, implying a role of alpha(2)beta(1) in platelet activation and a functional association with GPVI. These responses are also prevented by blocking integrin alpha(IIb)beta(3) and phosphoinositide 3-kinase, whereas aspirin treatment and ADP receptor blockade only, inhibit shape change. These results provide evidence for a PLCgamma2-independent collagen activation pathway requiring cooperation between GPVI and alpha(2)beta(1) leading to alpha(IIb)beta(3)-dependent aggregation and shape change by released ADP and thromboxane A(2). (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:53 / 59
页数:7
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