Endothelial cell prostacyclin synthesis induced by lymphocytes is independent of the membrane fatty acid composition of both cell types and of E-selectin, VCAM-1 or ICAM-1-mediated adhesion

Prostacyclin (PGI(2)), the main prostanoid in most vascular tissues regulat es haemostasis and vascular tone, as well as the proliferation of smooth mu scle cells. We have previously reported that lymphocyte contact with endoth elium enhances endothelial cell PGI(2) output. Here, we demonstrate the spe cificity of lymphocytes for switching on this response, Co-incubation of hu man umbilical vein endothelial cells (HUVEC) in serum-free medium with allo geneic peripheral blood lymphocytes (PBL), at a PBL:HUVEC ratio of 9:1, enh anced the basal (HUVEC alone) PGI(2) output by 25-fold under static conditi ons, and was not altered in conditions mimicking shear stress. It occurred without previous activation of either cell type and was dependent upon spec ific interactions with PBL. Indeed, the PGI(2) output induced by the co-inc ubation with resting neutrophils, non-activated platelets or latex beads wa s significantly lower than that induced by PBL. Blocking endothelial cell a dhesion molecules (EGAM) E-selectin, vascular cell adhesion molecule-1 (VCA M-1) or intracellular adhesion molecule-1 (ICAM-1) did not modify the PBL-i nduced PGI(2) output, although Cr-51-labelled PBL adhesion was significantl y decreased with anti-ICAM-1 antibody. Changes in the fatty acid compositio n of membrane phospholipids induced by incubation with eicosapentaenoic (EP A) or docosahexaenoic acids (DKA) resulted in diminished basal PGI(2) outpu t and adhesion of Cr-51-labelled PBL, whereas the PBL-stimulated PGI(2) out put was not modified. This specific cell-cell interaction represents a new stimulus for PGI(2) synthesis that does not primarily involve the ECAM path way, is independent of cell membrane fatty acid composition and shear stres s. This switch-on for PGI(2) synthesis, which is induced by lymphocytes, mi ght serve as a protection against atherogenesis.