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Title: | Physical proximity and functional interplay of PECAM-1 with the Fc receptor Fc gamma RIIa on the platelet plasma membrane. | Austin Authors: | Thai, Le M;Ashman, Leonie K;Harbour, Stacey N;Hogarth, P Mark;Jackson, Denise E | Affiliation: | Austin Research Institute, Austin Hospital, Studley Road, Heidelberg, Victoria, Australia 3084. | Issue Date: | 31-Jul-2003 | Publication information: | Blood 2003; 102(10): 3637-45 | Abstract: | We and others have recently defined that Platelet Endothelial Cell Adhesion Molecule-1 (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-1 may be physically and functionally associated with Fc gamma RIIa on the platelet membrane. The functional relationship between PECAM-1 and Fc gamma RIIa was assessed by determining the effect of anti-PECAM-1 monoclonal antibody Fab fragments on Fc gamma RIIa-mediated platelet aggregation and heparin-induced thrombocytopenia (HITS)-mediated platelet aggregation. Preincubation of washed platelets with monoclonal antibody fragments of 2BD4 directed against PECAM-1 and IV.3 directed against Fc gamma RIIa completely blocked Fc gamma RIIa-mediated platelet aggregation and HITS-mediated platelet aggregation, whereas anti-CD151 antibody had no blocking effect. Coengagement of Fc gamma RIIa and PECAM-1 resulted in negative regulation of Fc gamma RIIa-mediated phospholipase C gamma 2 activation, calcium mobilization, and phosphoinositide 3-kinase-dependent signaling pathways. In addition, the physical proximity of Fc gamma RIIa and PECAM-1 was confirmed by using fluorescence resonance energy transfer and coimmunoprecipitation studies. These results indicate that PECAM-1 and Fc gamma RIIa are colocalized on the platelet membrane and PECAM-1 down-regulates Fc gamma RIIa-mediated platelet responses. | Gov't Doc #: | 12893767 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/9528 | DOI: | 10.1182/blood-2003-02-0496 | Journal: | Blood | URL: | https://pubmed.ncbi.nlm.nih.gov/12893767 | Type: | Journal Article | Subjects: | Antibodies, Monoclonal.pharmacology Antigens, CD.metabolism.physiology Antigens, CD31.metabolism.physiology Blood Platelets.metabolism.physiology Calcium Signaling Cell Membrane.metabolism Heparin.pharmacology Humans Membrane Proteins.metabolism.physiology Peptide Fragments.immunology Phosphatidylinositol 3-Kinases.metabolism Phospholipase C gamma Platelet Adhesiveness.drug effects Protein Binding Receptors, IgG.metabolism.physiology Signal Transduction Type C Phospholipases.metabolism |
Appears in Collections: | Journal articles |
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