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British journal of pharmacology2002; 137(1); 107-117; doi: 10.1038/sj.bjp.0704834

Distinct roles of GPVI and integrin alpha(2)beta(1) in platelet shape change and aggregation induced by different collagens.

Abstract: 1. 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. 2. Bovine collagen types I-V, native equine tendon collagen fibrils and collagen-related peptide (CRP) all induced platelet aggregation and shape change. 3. Responses were abolished in FcRgamma chain-deficient platelets, which also lack GPVI, indicating a critical dependence on the GPVI/FcRgamma chain complex. 4. Responses to all collagens were unaffected in CD36-deficient platelets. 5. A monoclonal antibody (6F1) which binds to the alpha(2) 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. 6. Simultaneous blockade of the P2Y(1) and P2Y(12) receptors, and inhibition of cyclo-oxygenase demonstrated that CRP can activate platelets independently of ADP and TxA(2); however, responses to the collagens were dependent on these mediators. 7. This study confirms the importance of the GPVI/FcRgamma 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 alpha(2)beta(1), the significance of which depends on the collagen preparation.
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Publication Date: 2002-08-17 PubMed ID: 12183336PubMed Central: PMC1573462DOI: 10.1038/sj.bjp.0704834Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article examines the different roles of the GPVI and integrin alpha(2)beta(1) membrane proteins in the shape change and aggregation (clumping together) of blood platelets induced by different types of collagen. The study reveals the critical role of GPVI, a platelet membrane glycoprotein, in platelet response to collagen and the modulatory role of integrin alpha(2)beta(1).

Research Methodology and Findings

  • The authors conducted tests on a variety of collagen types, including types I-V from bovine sources, native equine tendon collagen fibrils, and collagen-related peptide (CRP), to gauge their ability to activate blood platelets. The results confirmed the power of these collagen types to induce platelet aggregation and shape change.
  • The team used platelets lacking the FcRgamma chain, which also lack GPVI, to investigate platelet response mechanisms. They found that these responses were removed, indicating that the GPVI/FcRgamma chain complex plays a vital role in activating platelets.
  • The study also explored platelets deficient in CD36, another membrane protein. The responses to all types of collagen were not affected in these platelets, ruling out the role of CD36 in this context.
  • The research also dealt with the action of a monoclonal antibody called 6F1, which binds to the alpha(2) integrin subunit of human platelets. This antibody affected the rate of the collagen-induced aggregation and onset, but its effects varied depending on the type of collagen used.
  • The researchers also blocked the P2Y(1) and P2Y(12) receptors, and inhibited the cyclo-oxygenase, to see if the CRP induces platelet activation independently of ADP and TxA(2). The findings confirm that while CRP can activate platelets independently, the responses to other collagens were dependent on these mediators.

Significant Conclusions

  • From the study, it is clear that the GPVI/FcRgamma chain complex has a significant role in platelet responses, regardless of the type of collagen inducing the response. This denies the existence of collagen type-specific receptors.
  • The research also throws light on the modulatory function of integrin alpha(2)beta(1), showing that its significance depends on the type of collagen involved.

Cite This Article

APA
Jarvis GE, Atkinson BT, Snell DC, Watson SP. (2002). Distinct roles of GPVI and integrin alpha(2)beta(1) in platelet shape change and aggregation induced by different collagens. Br J Pharmacol, 137(1), 107-117. https://doi.org/10.1038/sj.bjp.0704834

Publication

British journal of pharmacology
ISSN: 0007-1188
NlmUniqueID: 7502536
Country: England
Language: English
Volume: 137
Issue: 1
Pages: 107-117

Researcher Affiliations

Jarvis, Gavin E
  • Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT. gavin.jarvis@pharmacology.oxford.ac.uk
Atkinson, Ben T
    Snell, Daniel C
      Watson, Steve P

        MeSH Terms

        • Adenosine Diphosphate / physiology
        • Animals
        • Antibodies, Monoclonal / metabolism
        • Blood Platelets / cytology
        • Blood Platelets / drug effects
        • Blood Platelets / physiology
        • CD36 Antigens / metabolism
        • CD36 Antigens / physiology
        • Cattle
        • Cell Size
        • Collagen / metabolism
        • Collagen / pharmacology
        • Feedback, Physiological
        • Humans
        • In Vitro Techniques
        • Integrin alpha2beta1 / metabolism
        • Integrin alpha2beta1 / physiology
        • Membrane Proteins
        • Mice
        • Microscopy, Electron
        • Platelet Activation
        • Platelet Aggregation / drug effects
        • Platelet Aggregation / physiology
        • Platelet Membrane Glycoproteins / deficiency
        • Platelet Membrane Glycoproteins / physiology
        • Purinergic P2 Receptor Antagonists
        • Receptors, Collagen / metabolism
        • Receptors, Purinergic P2Y1
        • Receptors, Purinergic P2Y12
        • Thromboxane A2 / antagonists & inhibitors
        • Thromboxane A2 / biosynthesis

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