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.

Abstract

Prostacyclin (PGI2), the main prostanoid in most vascular tissues regulates haemostasis and vascular tone, as well as the proliferation of smooth muscle cells. We have previously reported that lymphocyte contact with endothelium enhances endothelial cell PGI2 output. Here, we demonstrate the specificity of lymphocytes for switching on this response. Co-incubation of human umbilical vein endothelial cells (HUVEC) in serum-free medium with allogeneic peripheral blood lymphocytes (PBL), at a PBL:HUVEC ratio of 9:1, enhanced the basal (HUVEC alone) PGI2 output by 2.5-fold under static conditions, and was not altered in conditions mimicking shear stress. It occurred without previous activation of either cell type and was dependent upon specific interactions with PBL. Indeed, the PGI2 output induced by the co-incubation with resting neutrophils, non-activated platelets or latex beads was significantly lower than that induced by PBL. Blocking endothelial cell adhesion molecules (ECAM) E-selectin, vascular cell adhesion molecule-1 (VCAM-1) or intracellular adhesion molecule-1(ICAM-1) did not modify the PBL-induced PGI2 output, although 51Cr-labelled PBL adhesion was significantly decreased with anti-ICAM-1 antibody. Changes in the fatty acid composition of membrane phospholipids induced by incubation with eicosapentaenoic (EPA) or docosahexaenoic acids (DHA) resulted in diminished basal PGI2 output and adhesion of 51Cr-labelled PBL, whereas the PBL-stimulated PGI2 output was not modified. This specific cell-cell interaction represents a new stimulus for PGI2 synthesis that does not primarily involve the ECAM pathway, is independent of cell membrane fatty acid composition and shear stress. This switch-on for PGI2 synthesis, which is induced by lymphocytes, might serve as a protection against atherogenesis.