Several investigators have demonstrated that endothelial cells have heterogeneous
intrinsic properties depending on their vascular origin. In this respect, very limited
knowledge exists concerning the production of eicosanoids by human microvascular endothelial
cells (HMEC). The aim of this study was to determine: 1) the pattern of the production
of cyclooxygenase metabolites by cultured HMEC from omental adipose tissue as compared
to the classical study of human umbilical vein endothelial cells (HUVEC); 2) the modification
of this metabolism upon leukotrienes (LTs) stimulation. Cultured HMEC produced prostaglandin
(PG) E2, PGF2 , 6-keto-PGF1 , and PGD2 (measured by enzymoimmunoassay). In basal conditions, PGD2 was the main product released in the supernatant. Upon stimulation with thrombin,
arachidonic acid and calcium ionophore A23187, a marked increase in the production
of PGE2, PGF2 , and 6-keto-PGFj , was observed; these results were quite different from HUVEC.
In contrast, PGD2 remained unchanged under our experimental conditions and thromboxane B2 was always undetectable. In all cases, the release of PGE2 and PGF2 , was higher than that of 6-keto-PGFj . A considerable amount of the metabolites
produced remained cell-associated. The total production (release + cell bound) of
cyclooxygenase products was stimulated by LTC4 and LTD4 in a dose-dependent manner (10-9 to 10-6 M). The production of PGD2 was unchanged. LTC4 and LTD4 were almost equally potent, but LTB4 was unable to stimulate PG synthesis (n=4). The production of metabolites induced
by 1 uM LTC4 or LTD4 was even higher than that obtained in the presence of high concentrations of thrombin
(5 U/ml). This contrasted with the more pronounced stimulation of thrombin on HUVEC
as compared to LTs. In the kinetic studies (n=2) we have observed a slow time-course
of release of PGE2 and 6-keto-PGF1 into the supernatant of LTs-stimulated HMEC (half-maximal formation
at 14-15 min). The stimulatory activity of LTC4 and LTD4 on the production of vasoactive cyclooxygenase metabolites by HMEC could be relevant
in inflammatory processes.
