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(Journal of Leukocyte Biology. 2000;68:881-889.)
© 2000 by Society for Leukocyte Biology

Human lymphocytes stimulate prostacyclin synthesis in human umbilical vein endothelial cells. Involvement of endothelial cPLA₂

Faten Merhi-Soussi, Zury Dominguez, Olga Macovschi, Madeleine Dubois, Alain Savany, Michel Lagarde and Annie-France Prigent

INSERM U352, Laboratoire de Biochimie et Pharmacologie, Institut National des Sciences Appliquées de Lyon, Villeurbanne, France; and
Cátedra de Patología General y Fisiopatología, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas

Correspondence: Annie-France Prigent, INSERM U352, Laboratoire de Biochimie et Pharmacologie, Bâtiment 406, Institut National des Sciences Appliquées de Lyon, 20 avenue Albert Einstein, 69621 Villeurbanne Cedex, France. E-mail: prigent{at}insa.insa-lyon.fr

Prostacyclin (PGI₂) contributes to the maintenance of a nonadhesive luminal surface in blood vessels due to its anti-platelet and vasodilatory properties. Here, we sought to determine whether peripheral blood lymphocytes (PBL) may regulate the PGI₂ production of human umbilical vein endothelial cells (HUVEC). Cell-cell contact between HUVEC and lymphocytes markedly enhanced PGI₂ synthesis as a function of the number of lymphocytes added. This stimulated synthesis was totally suppressed when lymphocytes and HUVEC were separated by a microporous insert. It was not due to prostaglandin H synthase up-regulation. The pretreatment of lymphocytes with the PGI₂ synthase inhibitor tranylcypromine partially inhibited PGI₂ synthesis (47%), suggesting a transcellular metabolism of the endothelial prostaglandin endoperoxide PGH₂ by the lymphocyte PGI₂ synthase. Experiments using [¹⁴C]arachidonate-labeled lymphocytes coincubated with unlabeled HUVEC, and [¹⁴C]arachidonate-labeled HUVEC coincubated with unlabeled lymphocytes showed that the arachidonic acid used for PGI₂ synthesis was totally of endothelial origin. Furthermore, the PGI₂ synthesis was strongly inhibited by the cytosolic phospholipase A₂ inhibitor, MAFP and totally suppressed by the combination of the calcium chelators, BAPTA and EGTA. Collectively, these results suggest that lymphocytes trigger an outside-in signaling in endothelial cells involving cPLA₂ activation. Overall, the switch-on for PGI₂ synthesis induced by lymphocytes might serve as a protection against atherothrombogenesis.

Key Words: lymphocyte-endothelial cell interactions • prostaglandin H and prostaglandin I₂ synthases • atherothrombogenesis

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