Please use this identifier to cite or link to this item:
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
DOI: 10.1182/blood-2003-02-0496
Type: Journal Article
Subjects: Antibodies, Monoclonal.pharmacology
Antigens, CD.metabolism.physiology
Antigens, CD31.metabolism.physiology
Blood Platelets.metabolism.physiology
Calcium Signaling
Cell Membrane.metabolism
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

Show full item record

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.