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Physical proximity and functional interplay of PECAM-1 with the Fc receptor Fc gamma RIIa on the platelet plasma membrane
- Source :
- Blood. 102(10)
- Publication Year :
- 2003
-
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-γ chain) signaling pathway.1,2 In this study, we hypothesized that PECAM-1 may be physically and functionally associated with FcγRIIa on the platelet membrane. The functional relationship between PECAM-1 and FcγRIIa was assessed by determining the effect of anti-PECAM-1 monoclonal antibody Fab fragments on FcγRIIa-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 FcγRIIa completely blocked FcγRIIa-mediated platelet aggregation and HITS-mediated platelet aggregation, whereas anti-CD151 antibody had no blocking effect. Coengagement of FcγRIIa and PECAM-1 resulted in negative regulation of FcγRIIa-mediated phospholipase Cγ2 activation, calcium mobilization, and phosphoinositide 3-kinase-dependent signaling pathways. In addition, the physical proximity of FcγRIIa and PECAM-1 was confirmed by using fluorescence resonance energy transfer and coimmunoprecipitation studies. These results indicate that PECAM-1 and FcγRIIa are colocalized on the platelet membrane and PECAM-1 down-regulates FcγRIIa-mediated platelet responses. (Blood. 2003;102:3637-3645)
- Subjects :
- Blood Platelets
medicine.drug_class
Immunology
Fc receptor
Phospholipase C gamma
Monoclonal antibody
Biochemistry
Phosphatidylinositol 3-Kinases
Platelet Adhesiveness
Antigens, CD
Platelet adhesiveness
medicine
Humans
Platelet
Calcium Signaling
Receptor
biology
Chemistry
Heparin
Cell Membrane
Receptors, IgG
Antibodies, Monoclonal
Membrane Proteins
Cell Biology
Hematology
Peptide Fragments
Cell biology
Platelet Endothelial Cell Adhesion Molecule-1
Type C Phospholipases
embryonic structures
cardiovascular system
biology.protein
GPVI
Antibody
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 00064971
- Volume :
- 102
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....d1dff54ffb693cffe4641fc7f0d148d9