Molecular Analysis of Platelet-Immunocyte Interaction

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We have examined the effect of inflammatory cytokines on the platelet activation. IL-beta and IFN-gamma were found to enhance the adhesion of thrombin-treated platelets to moncytic leukemia cells(U937),when the adhesion was assayed by platelet-mediated cell agglutination. The agglutination was inhibited by a monoclonal anti-P-selectin antibody or EDTA,suggesting that the enhanced platelet adhesion to the leukemic cells was mediated by P-selectin. In addition,these cytokines also increased the release of 5-HT from platelets in the presence of a low concentration of thrombin. These data suggest that platelet functions are regulated by the cytokines and that activated platelets participate in inflammatory process. We next examined the possibility that leukocytes are functionally modified by their adhesion to activated platelets. We used human peripheral blood monocytes and neutrophils and measured superoxide anion generation by these cells cultured with platelets. The levels of superoxide anion production was found to be markedly elevated when thrombin-activated platelets were used.This enhancement was not observed when cultured with resting platelets. The increase depended on incubation time and platelet concentration. The membranes prepared from activated platelets also induced superoxide anion production,but the culture supernatant of activated platelets did not. The enhanced superoxide anion production was inhibited by anti-P-selectin antibody,anti-sialyl-Le^X antibody or a soluble recombinant P-selectin-glutathione-S-transferase(GST) fusion protein. These results indicate that the adhesion of activate dplatelets to the leukocytes through P-selectin was a crucial step for the activation of leukocyte function, and support the idea that activated platelets are actively involved in inflammation processes.