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A PLCγ2‐independent platelet collagen aggregation requiring functional association of GPVI and integrin α 2 β 1
Author(s) -
Mangin P,
ne C,
Eckly A,
Ohlmann P,
Freund M,
Nieswandt B,
Cazenave J-P,
Gachet C,
Lanza F
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00337-5
Subject(s) - gpvi , collagen receptor , integrin , platelet , chemistry , platelet activation , platelet membrane glycoprotein , platelet glycoprotein gpiib iiia complex , thromboxane a2 , thromboxane , microbiology and biotechnology , receptor , biochemistry , immunology , biology
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 α 2 β 1 and GPVI each inhibit the residual collagen response, implying a role of α 2 β 1 in platelet activation and a functional association with GPVI. These responses are also prevented by blocking integrin α IIb β 3 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 α 2 β 1 leading to α IIb β 3 ‐dependent aggregation and shape change by released ADP and thromboxane A 2 .