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

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Abstract
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 αIIbβ3 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 αIIbβ3‐dependent aggregation and shape change by released ADP and thromboxane A2.