MONOCYTIC-ENDOTHELIAL CELL-INTERACTION - REGULATION OF PROSTANOID SYNTHESIS IN HUMAN COCULTURE

Coculture of a monocytic cell line (HL-60) and iliacal endothelial cel ls as an in vitro model of vascular inflammation was investigated for cooperative regulatory mechanisms of prostanoid synthesis under condit ions of selective prestimulation, ln coculture of endothelial cells an d 12-O-tetradecanoylphorbol 13-acetate (TPA)-prestimulated monocytic: HL-60 cells the capacity of prostanoid synthesis from arachidonic acid was strongly increased compared with monocultures. Concomitant with u p-regulation of specific adhesion molecules, cyclooxygenase (COX) 2 mR NA was induced in endothelial cells in coculture independent of cell c ontact, HL-60 cells exhibited no alterations in mRNA expression of cyc looxygenases or thromboxane synthase, Coculture of TPA-prestimulated e ndothelial cells with unstimulated HL-60 cells led to a selectively in creased capacity of thromboxane production, Under this condition HL-60 cells up-regulated COX1 and COX2 mRNA, whereas endothelial mRNA level s did not change, Our data demonstrate that the increase in prostanoid synthesis in coculture essentially depends on rapid induction of COX2 mRNA within 2 h.