Human lymphocytes stimulate prostacyclin synthesis in human umbilical veinendothelial cells. Involvement of endothelial cPLA(2)

Prostacyclin (PGI(2)) contributes to the maintenance of a nonadhesive lumin al surface in blood vessels due to its anti-platelet and vasodilatory prope rties. Here, we sought to determine whether peripheral blood lymphocytes (P BL) may regulate the PGI(2) production of human umbilical vein endothelial cells (HUVEC), Cell-cell contact between HUVEC and lymphocytes markedly enh anced PGI(2) synthesis as a function of the number of lymphocytes added. Th is stimulated synthesis tvas totally suppressed when lymphocytes and HUVEC were separated by a microporous insert, It was not due to prostaglandin H s ynthase up-regulation. The pretreatment of lymphocytes with the PGI(2) synt hase inhibitor tranylcypromine partially inhibited PGI(2) synthesis (47%), suggesting a transcellular metabolism of the: endothelial prostaglandin end operoxide PGH(2) by the lymphocyte PGI(2) synthase, Experiments using [C-14 ]arachidonate-labeled lymphocytes coincubated with unlabeled HUVEC, and [C- 14]arachidonate-labeled HUVEC coincubated with unlabeled lymphocytes showed that the arachidonic acid used for PGI(2) synthesis was totally of endothe lial origin. Furthermore, the PGI(2) synthesis was strongly inhibited by th e cytosolic phospholipase A(2) inhibitor, MAFP and totally suppressed by th e combination of the calcium chelators, BAPTA and EGTA, Collectively, these results suggest that lymphocytes trigger an outside-in signaling in endoth elial cells involving cPLA(2) activation, Overall, the switch-on for PGI(2) synthesis induced by lymphocytes might serve as a protection against ather othrombogenesis.