Activation of human platelets by exposure to a monoclonal antibody, PM6/248, to glycoprotein IIb-IIIa.
Monoclonal antibody PM6/248, which recognizes the GPIIb-IIIa complex on human platelets, causes platelet aggregation in platelet-rich plasma or in gel-filtered platelet suspensions. Aggregation follows a concentration-dependent lag phase and reaches a maximum at 8 micrograms/ml. High concentrations of antibody (less than 30 micrograms/ml) produce complete inhibition of the aggregation response. Aggregation is accompanied by serotonin secretion and thromboxane A2 synthesis, neither of which are inhibited by high concentrations of antibody, and by the mobilization of intracellular Ca2+. The F(ab')2 fragment of PM6/248 does not cause platelet activation and pre-incubation of platelets with this fragment inhibits all platelet responses stimulated by the whole antibody. Pre-incubation with the F(ab')2 fragment of the anti-Fc gamma RII Mab, IV. 3, also inhibits all responses to PM6/248. These data indicate that platelet activation stimulated by PM6/248 is caused by cross-linking of GPIIb-IIIa to the Fc gamma RII which stimulates signal transduction across the plasma membrane through a conformational change in the Fc gamma RII.
Hornby
E J
EJ
Department of Peripheral Pharmacology, Glaxo Group Research, Ware, Hertfordshire.
Brown
S
S
Wilkinson
J M
JM
Mattock
C
C
Authi
K S
KS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002118:Calcium / Q000097:blood; D015151:Immunoblotting; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015539:Platelet Activation / Q000276:immunology*; D010974:Platelet Aggregation / Q000276:immunology; D010980:Platelet Membrane Glycoproteins / Q000276:immunology*; D012701:Serotonin / Q000097:blood; D013929:Thromboxane B2 / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D010980:Platelet Membrane Glycoproteins; D012701:Serotonin; D013929:Thromboxane B2; D002118:Calcium