Distinct roles of GPVI and integrin α2β1 in platelet shape change and aggregation induced by different collagens

Article date: September 2002

By: Gavin E Jarvis, Ben T Atkinson, Daniel C Snell, Steve P Watson in Volume 137, Issue 1, pages 107-117

Various platelet membrane glycoproteins have been proposed as receptors for collagen, in some cases as receptors for specific collagen types. In this study we have compared the ability of a range of collagen types to activate platelets.

Bovine collagen types I–V, native equine tendon collagen fibrils and collagen‐related peptide (CRP) all induced platelet aggregation and shape change.

Responses were abolished in FcRγ chain‐deficient platelets, which also lack GPVI, indicating a critical dependence on the GPVI/FcRγ chain complex.

Responses to all collagens were unaffected in CD36‐deficient platelets.

A monoclonal antibody (6F1) which binds to the α2 integrin subunit of human platelets had a minimal effect on the rate and extent of aggregation induced by the collagens; however, it delayed the onset of aggregation following addition of all collagens. For shape change, 6F1 abolished the response induced by collagen types I and IV, substantially attenuated that to collagen types II, III and V, but only partially inhibited Horm collagen.

Simultaneous blockade of the P2Y1 and P2Y12 receptors, and inhibition of cyclo‐oxygenase demonstrated that CRP can activate platelets independently of ADP and TxA2; however, responses to the collagens were dependent on these mediators.

This study confirms the importance of the GPVI/FcRγ chain complex in platelet responses induced by a range of collagen agonists, while providing no evidence for collagen type‐specific receptors. It also provides evidence for a modulatory role of α2β1, the significance of which depends on the collagen preparation.

Various platelet membrane glycoproteins have been proposed as receptors for collagen, in some cases as receptors for specific collagen types. In this study we have compared the ability of a range of collagen types to activate platelets.

Bovine collagen types I–V, native equine tendon collagen fibrils and collagen‐related peptide (CRP) all induced platelet aggregation and shape change.

Responses were abolished in FcRγ chain‐deficient platelets, which also lack GPVI, indicating a critical dependence on the GPVI/FcRγ chain complex.

Responses to all collagens were unaffected in CD36‐deficient platelets.

A monoclonal antibody (6F1) which binds to the α2 integrin subunit of human platelets had a minimal effect on the rate and extent of aggregation induced by the collagens; however, it delayed the onset of aggregation following addition of all collagens. For shape change, 6F1 abolished the response induced by collagen types I and IV, substantially attenuated that to collagen types II, III and V, but only partially inhibited Horm collagen.

Simultaneous blockade of the P2Y1 and P2Y12 receptors, and inhibition of cyclo‐oxygenase demonstrated that CRP can activate platelets independently of ADP and TxA2; however, responses to the collagens were dependent on these mediators.

This study confirms the importance of the GPVI/FcRγ chain complex in platelet responses induced by a range of collagen agonists, while providing no evidence for collagen type‐specific receptors. It also provides evidence for a modulatory role of α2β1, the significance of which depends on the collagen preparation.

British Journal of Pharmacology (2002) 137, 107–117. doi:10.1038/sj.bjp.0704834

DOI: 10.1038/sj.bjp.0704834

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