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

FEBS Letters

Cazenave, J-P¹  Ohlmann, P¹  Freund, M¹  Gachet, C¹  Mangin, P¹  Eckly, A¹  Nieswandt, B²  Nonne, C¹  Lanza, F¹ 

[1] INSERM U.311, Etablissement Français du Sang-Alsace, 10 rue Spielmann, BP 36, 67065 Strasbourg Cedex, France;Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany

关键词: Collagen;    Integrin α2β1;    Phospholipase C-γ2;    Knockout mouse;    Platelet;    Signal transduction;    CRP;    collagen-related peptide;    GP;    glycoprotein;    Ig;    immunoglobulin;    mAb;    monoclonal antibody;    PI3K;    phosphoinositide 3-kinase;    PLC;    phospholipase C;    vWF;    von Willebrand factor;   

DOI  :  10.1016/S0014-5793(03)00337-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The role of the phospholipase C (PLC)γ2 isotype in platelet activation was evaluated by studying PLCγ2 −/− mice. These mice have a prolonged bleeding time but their platelets respond normally to non-collagenous agonists. PLCγ2-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 α₂β₁ and GPVI each inhibit the residual collagen response, implying a role of α₂β₁ in platelet activation and a functional association with GPVI. These responses are also prevented by blocking integrin α_IIbβ₃ and phosphoinositide 3-kinase, whereas aspirin treatment and ADP receptor blockade only inhibit shape change. These results provide evidence for a PLCγ2-independent collagen activation pathway requiring cooperation between GPVI and α₂β₁ leading to α_IIbβ₃-dependent aggregation and shape change by released ADP and thromboxane A₂.

【 授权许可】

Unknown