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


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 PLCgamma2 being identified among the list of tyrosine phosphorylated proteins. As collagen activates platelet through the GPVI-Fc receptor gamma-chain (FcRgamma) complex, we used FcRgamma 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 FcRgamma null platelets and markedly reduced in the absence of PLCgamma2. 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.
Riba
R
R
Centre for Atherothrombosis Research, University of Bradford, Bradford, UK.
Hughes
C E
CE
Graham
A
A
Watson
S P
SP
Naseem
K M
KM
D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D010766:Phosphorylation; D015539:Platelet Activation; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D020033:Protein Isoforms; D011961:Receptors, Fc / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology
D052242:Adiponectin; D010980:Platelet Membrane Glycoproteins; D020033:Protein Isoforms; D011961:Receptors, Fc; C098341:platelet membrane glycoprotein VI