Globular adiponectin induces platelet activation through the collagen receptor GPVI-Fc receptor γ chain complex

Watson, S. P.; Naseem, Khalid M.; Riba, R.; Hughes, C. E.; Graham, A.; Watson, S. P.; Naseem, K. M.

Abstract

Background: The adipocyte-derived cytokine, adiponectin (Ad), exerts potent vascular effects, although the direct effects of Ad on blood platelets are unclear. Objective: The influence of globular Ad (gAd) on blood platelet function was investigated. Research design and methods: We measured platelet aggregation and tyrosine phosphorylation signaling events in human and mouse platelets. The ability of gAd to activate Glycoprotein VI (GPVI) activity was determined with a NFAT luciferase reporter assay. Results: gAd, but not full length Ad, induced rapid aggregation and granule secretion of human and mouse platelets through a pathway that is ablated under conditions of Src kinase inhibition, indicating a tyrosine kinase-dependent mechanism. Consistent with this, gAd stimulates rapid tyrosine phosphorylation of several proteins in human and mouse platelets. The pattern of increase in tyrosine phosphorylation was similar to that induced by collagen, with the tyrosine kinase Syk and PLCγ2 being identified among the list of tyrosine phosphorylated proteins. As collagen activates platelet through the GPVI-Fc receptor γ-chain (FcRγ) complex, we used FcRγ null platelets (which also lack GPVI) to explore the mechanism by which gAd stimulates platelets. Stimulation of tyrosine phosphorylation and platelet aggregation by gAd was abolished in FcRγ null platelets and markedly reduced in the absence of PLCγ2. Further, GPVI was confirmed as a collagen receptor for gAd by increased luciferase activity in Jurkat T-cells transfected with GPVI. Conclusions: We identify gAd as a novel ligand for GPVI that stimulates tyrosine kinase-dependent platelet aggregation. Our data raise the possibility that gAd may promote unwanted platelet activation at sites of vascular injury.

Citation

Riba, R., Hughes, C. E., Graham, A., Watson, S. P., & Naseem, K. M. (2008). Globular adiponectin induces platelet activation through the collagen receptor GPVI-Fc receptor γ chain complex. Journal of thrombosis and haemostasis : JTH, 6(6), 1012-1020. https://doi.org/10.1111/j.1538-7836.2008.02982.x

• Journal Article Type: Article
• Acceptance Date: Mar 25, 2008
• Online Publication Date: Apr 17, 2008
• Publication Date: Jun 1, 2008
• Deposit Date: Nov 13, 2014
• Journal: Journal Of Thrombosis And Haemostasis
• Print ISSN: 1538-7933
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 6
• Pages: 1012-1020
• DOI: https://doi.org/10.1111/j.1538-7836.2008.02982.x
• Keywords: Adiponectin; Collagen; Glycoprotein VI; Platelets; Signaling; Src kinases
• Public URL: https://hull-repository.worktribe.com/output/468179
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1538-7836.2008.02982.x
• Contract Date: Nov 23, 2017