Lipoxins stimulate prostacyclin generation by human endothelial cells

Abstract

Cultured human umbilical endothelial cells were incubated with lipoxins and their ability to generate prostacyclin (PGI₂) was assessed and compared to that induced by either leukotriene C₄ or an ionophore of divalent cations (A-23,187). When exposed to either lipoxin A₄, lipoxin B₄, or 7-cis, 11-trans-lipoxin A₄, endothelial cells generated prostacyclin detected as 6-keto-PGF_1α. Of the lipoxins examined, 7-cis, 11-trans-lipoxin A₄ proved to be the most effective with PGI₂ production twice that induced by equimolar amounts of A-23,187 (5 μM). On a molar basis, lipoxin A₄ and lipoxin B₄ were less potent than leukotriene C₄ although they were more efficacious. When either lipoxin A₄ or lipoxin B₄ was added to cells simultaneously with leukotriene C₄, the formation of prostacyclin was greater than that induced by leukotriene C₄ alone. During the time course of exposure to lipoxins (0–20 min, 37°C), cultured endothelial cells did not further transform these compounds via ω-oxidation as determined by reverse-phase HPLC. These data indicate that lipoxins can stimulate PGI₂ generation by human endothelial cells. Moreover, they suggest a role for these lipoxygenase products of arachidonic acid in the regulation of hemostasis, inflammation and vascular reactivity.