Allogenic induction of thromboplastin synthesis in monocytes and endothelial cells. Biphasic effect of cyclosporin A.

Monocytes and endothelial cells were stimulated in co-culture with allogeneic lymphocytes to produce thromboplastin (TPL). The induction was biphasic, an early response (8-24 h) was greatly augmented by cyclosporin A (CS) (0.5-5 micrograms/ml) whereas the late response (day 3-4) was inhibited. Prednisolone inhibited both responses. Both drugs inhibited lymphocyte proliferation. Interferon-gamma decreased MLC TPL activity but increased thymidine incorporation. CD4+ cells were instrumental in inducing the early TPL peak in monocytes, whereas CD8+ cells decreased the TPL effect. With endothelial cells both T cell classes were equally effective. Conditioned medium from MLC as well as from co-cultures of endothelial cells and lymphocytes induced early TPL synthesis in endothelial cells. Upon allogeneic stimulation monocytes, but not endothelial cells, produced a significant amount of F-VII, most of which was apparently undercarboxylated.