Lipoxins stimulate prostacyclin generation by human endothelial cells (original) (raw)

Cultured human umbilical endothelial cells were incubated with lipoxins and their ability to generate prostacyclin (PGI,) was assessed and compared to that induced by either leukotriene C, or an ionophore of divalent cations (A-23,187). When exposed to either lipoxin 4, lipoxin B4, or 'I-cis.1 I-truns-lipoxin 4, endothelial cells generated prostacyclin detected as 6-keto-PGF,,. Of the lipoxins examined, 'I-c&l I-trans-lipoxin A., proved to be the most effective with PGI, production twice that induced by equimolar amounts of A-23,187 (5 PM). On a molar basis, lipoxin A., and lipoxin B4 were less potent than leukotriene C, although they were more efficacious. When either lipoxin A., or lipoxin B4 was added to cells simultaneously with leukotriene C,, the formation of prostacyclin was greater than that induced by leukotriene C, alone. During the time course of exposure to lipoxins (O-20 min, 37"C), cultured endothelial cells did not further transform these compounds via o-oxidation as determined by reverse-phase HPLC. These data indicate that lipoxins can stimulate PGI, generation by human endothelial cells. Moreover, they suggest a role for these lipoxygenase products of arachidonic acid in the regulation of hernostasis, inflammation and vascular reactivity. Arachidonic acid; Lipoxygenase product