Evidence for cross-talk between glycoprotein VI and Gi-coupled receptors during collagen-induced platelet aggregation

被引:78
作者
Nieswandt, B
Bergmeier, WG
Eckly, A
Schulte, V
Ohlmann, P
Cazenave, JP
Zirngibl, H
Offermanns, S
Gachet, C
机构
[1] INSERM, U331, Etab Francais Sang Alsace, Strasbourg, France
[2] Heidelberg Univ, Dept Mol Pharmacol, Heidelberg, Germany
[3] Univ Witten Herdecke, Dept Mol Oncol, D-42117 Wuppertal, Germany
关键词
D O I
10.1182/blood.V97.12.3829
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Collagen-induced platelet aggregation is a complex process and involves synergistic action of integrins, immunoglobulin (19)-like receptors, G-proteincoupled receptors and their ligands, most importantly collagen itself, thromboxane A(2) (TXA(2)), and adenosine diphosphate (ADP), The precise role of each of these receptor systems in the overall processes of activation and aggregation, however, Is still poorly defined. Among the collagen receptors expressed on platelets, glycoprotein (GP) VI has been identified to play a crucial role in collagen-induced activation. GPVI is associated with the FcR gamma chain, which serves as the signal transducing unit of the receptor complex. It is well known that clustering of GPVI by highly specific agonists results in platelet activation and irreversible aggregation, but it is unclear whether collagen has the same effect on the receptor. This study shows that platelets from G alphaq-deficient mice, despite their severely impaired response to collagen, normally aggregate on clustering of GPVI, suggesting this not to be the principal mechanism by which collagen activates platelets. On the other hand, dimerization of GPVI by a monoclonal antibody (JAQ1), which by itself did not induce aggregation, provided a sufficient stimulus to potentiate platelet responses to Gi-coupled, but not Gq-coupled, agonists, The combination of JAQ1 and adrenaline or ADP, but not serotonin, resulted in alpha (llb)beta (3)-dependent aggregation that occurred without intracellular calcium mobilization and shape change in the absence of G alphaq or the P2Y(1) receptor. Together, these results provide evidence for a cross-talk between (dimerized) GPVI and Gi-coupled receptors during collagen-induced platelet aggregation.
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页码:3829 / 3835
页数:7
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