Enhanced expression of thrombomodulin by intracellular cyclic AMP-increasing agents in two human megakaryoblastic leukemia cell lines.

Functionally active thrombomodulin (TM) was expressed in human megakaryoblastic leukemia (MEG-01s) cells. We examined the effect of agents that increased the intracellular concentration of cAMP on the expression of TM by these cells. N6,O2-dibutyryl cAMP (dbcAMP) markedly enhanced TM antigen, activity, and mRNA level in MEG-01s cells. Other agents, 8-bromo-cAMP (8BrcAMP), forskolin, and prostaglandin E1 were also effective for the enhancement. Moreover, similar enhancement of TM by these agents was also observed in another human leukemia cell line, HEL, which has megakaryocytic markers. In contrast to the marked enhancement of TM expression by these agents, the expression of the other megakaryocytic markers including platelet glycoproteins IIb/IIIa, Ib, von Willebrand factor and beta-thromboglobulin was not stimulated in MEG-01s or HEL cells. These results suggest that expression of TM is rather specifically regulated by cAMP in human megakaryocytes.