EFFECT OF CEPHARANTHIN AND CYTOCHALASIN D ON PLATELET INTERNALIZATIONOF ANTI-GLYCOPROTEIN IIB IIIA ANTIBODIES/

The effects of cepharanthin and cytochalasin D on the internalization of anti-glycoprotein IIb/IIIa antibodies by platelets were investigate d in 13 patients with chronic immune thrombocytopenic purpura who had circulating anti-glycoprotein IIb/IIIa autoantibodies. Unfixed platele ts were incubated with a monoclonal anti-glycoprotein IIb/IIIa antibod y (NNKY1-32) or with platelet-binding IgG from the patients (which con tained anti-glycoprotein IIb/IIIa antibodies). Flow cytometry showed t hat the binding of NNKY1-32 to platelets was markedly decreased after incubation for 120 min compared with incubation for 10 min. This decre ase was inhibited by cepharanthin but not by cytochalasin D. Platelet- binding IgG also showed markedly reduced binding after incubation for 120 min compared with 10 min, and this decrease was inhibited by both cepharanthin and cytochalasin D. Cytochalasin D inhibits platelet cyto skeletal activity while cepharanthin does not. Therefore, our results suggest that the internalization of anti-glycoprotein IIb/IIIa antibod ies from the plasma of patients with immune thrombocytopenic purpura i s related to platelet cytoskeletal reorganization, while the cytoskelt on did not participate in internalization of the monoclonal anti-glyco protein IIb/IIIa antibody (NNKY1-32). Cepharanthin may be useful for s tudying the internalization and cycling of glycoprotein IIb/IIIa in hu man platelets, and it may also be potentially useful for the treatment of immune thrombocytopenic purpura.