Journal
BLOOD
Volume 102, Issue 10, Pages 3637-3645Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2003-02-0496
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We and others have recently defined that (P) under bar latelet (E) under bar ndothelial (C) under bar ell (A) under bar dhesion (M) under bar olecule-11 (PECAM-1/CD31) functions as a negative regulator of platelet-collagen interactions involving the glycoprotein VI/Fc: receptor gamma chain (GPVI/FcR-gamma chain) signaling pathway.(1,2) In this study, we hypothesized that PECAM-11 may be physically and functionally associated with FcgammaRIIa on the platelet membrane. The functional relationship between PECAM-1 and FcgammaRIIa was assessed by determining the effect of anti-PECAM-1 monoclonal antibody Fab fragments on FcgammaRlla-mediated platelet aggregation and heparin-induced thrombocytopenia (HITS)mediated platelet aggregation. Preincubation of washed platelets with monoclonal antibody fragments of 213134 directed against PECAM-1 and IV.3 directed against FcgammaRIIa completely blocked FcgammaRIIa-mediated platelet aggregation and HITS-mediated platelet aggregation, whereas anti-CD151 antibody had no blocking effect. Coengagement of FcgammaRIIa and PECAM-11 resulted in negative regulation of FcgammaRIIa-mediated phospholipase Cgamma2 activation, calcium mobilization, and phosphoinositide-3-kinase-dependent signaling pathways. In addition, the physical proximity of FcgammaRIIa and PECAM-1 was confirmed by using fluorescence resonance energy transfer and colmmunoprecipitation studies These results indicate that PECAM-1 and FcgammaRIIa are colocalized on the platelet membrane and PECAM-11 down-regulates FcgammaRIIa-medicated platelet responses.
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