Lipoxins stimulate prostacyclin generation by human endothelial cells

FEBS Letters

Nicolaou, K.C.³  Gimbrone, Michael A.²  Brezinski, Mark E.¹  Serhan, Charles N.¹ 

[1] Hematology Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA USA;Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA USA;Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA

关键词: Arachidonic acid;    Lipoxygenase product;    LXA4;    lipoxin A4;    5S;    6R;    15S-trihydroxy-7;    9;    13-trans-11-cis-eicosatetraenoic acid;    LXB4;    lipoxin B4;    5S;    14R;    15S-trihydroxy-6;    10;    12-trans-8-cis-eicosatetraenoic acid;    7-cis-11-trans-LXA4;    5S;    6R;    15S-trihydroxy-9;    11;    13-trans-7-cis-eicosatetraenoic acid;    PGI2;    prostacyclin;    RP-HPLC;    reverse-phase high-pressure liquid chromatography;   

DOI  :  10.1016/0014-5793(89)80214-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown