Lipoxins stimulate prostacyclin generation by human endothelial cells.
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-PGF1 alpha. 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 microM). 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 degrees C), cultured endothelial cells did not further transform these compounds via omega-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.
Brezinski
M E
ME
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Gimbrone
M A
MA
Nicolaou
K C
KC
Serhan
C N
CN
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007052:Ibuprofen / Q000494:pharmacology; D007700:Kinetics; D044045:Lipoxins; D013189:SRS-A / Q000494:pharmacology; D014471:Umbilical Veins
D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D013189:SRS-A; C040527:lipoxin A4; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; C042651:lipoxin B4; D011464:Epoprostenol; D007052:Ibuprofen