Interaction of two GPIIb/IIIa monoclonal antibodies with platelet Fc receptor (Fc gamma RII).
We have previously used the IV-3 monoclonal antibody specific for Fc gamma RII to demonstrate that platelet activation by CD9 monoclonal antibodies such as ALB-6 is mediated by the Fc gamma RII. Here, we show that platelet activation following addition of a monoclonal antibody directed against GPIIb/IIIa, P256 is completely blocked by IV-3, as monitored by serotonin release, calcium and pH modifications. However, aggregation was only partially inhibited. D3GP3 is another monoclonal antibody directed against GPIIIa which has been shown to induce platelet aggregation by exposure of the fibrinogen binding site. The present study demonstrates that this phenomenon is not accompanied by calcium flux or pH modification, nor is it blocked by pretreatment of platelet by IV-3. Despite its apparent independence from the Fc gamma RII activation pathway, D3GP3, but not its Fab fragment, was able to inhibit ALB-6 induced activation, including serotonin release, calcium flux and pH modifications. Binding studies demonstrated that D3GP3 (20 micrograms/ml, 0.13 microM) does not block ALB-6 binding to CD9 antigen but completely blocks IV-3 binding to the Fc receptor for concentrations of IV-3 ranging from 0 to 15 nM. Together, these results suggest an interaction between GPIIb/IIIa, Fc gamma RII and GPIIb/IIIa monoclonal antibodies which in some cases can result in activation of platelets through Fc gamma RII.
Rubinstein
E
E
Department of Medical Biology, University of Tennessee Medical Center, Knoxville 37920.
Kouns
W C
WC
Jennings
L K
LK
Boucheix
C
C
Carroll
R C
RC
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000097:blood; D006801:Humans; D015539:Platelet Activation / Q000276:immunology*; D010974:Platelet Aggregation / Q000276:immunology; D010980:Platelet Membrane Glycoproteins / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D012701:Serotonin / Q000097:blood
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D010980:Platelet Membrane Glycoproteins; D011961:Receptors, Fc; D017452:Receptors, IgG; D012701:Serotonin; D002118:Calcium