LIPOXINS STIMULATE PROSTACYCLIN GENERATION BY HUMAN-ENDOTHELIAL CELLS

LIPOXINS STIMULATE PROSTACYCLIN GENERATION BY HUMAN-ENDOTHELIAL CELLS
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DOI:
10.1016/0014-5793(89)80214-5
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发表时间:
1989-03-13
期刊:
影响因子:
3.5
通讯作者:
SERHAN, CN
SERHAN, CN
中科院分区:
生物学3区
文献类型:
--
作者:
BREZINSKI, ME;GIMBRONE, MA;SERHAN, CN

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将培养的人脐带内皮细胞与脂毒素孵育,评估其生成前列环素(PGI2)的能力,并与白三烯c4或二价阳离子离子载体诱导的能力进行比较(A‐23,187)。当暴露于脂素A4、脂素B4或7‐顺式、11‐反式脂素A4时,内皮细胞产生的前列环素被检测为6‐酮- PGF1α。在所检测的脂素中,7‐顺式、11‐反式脂素a4被证明最有效,其pgi2的产生是等摩尔量A‐23,187 (5 μM)诱导的两倍。在摩尔基础上,脂素a4和脂素b4的效力低于白三烯c4,尽管它们更有效。当脂素a4或脂素b4与白三烯C4同时加入细胞时,前列环素的形成比单独加入白三烯C4诱导的要多。在暴露于脂毒素的时间过程中(0-20分钟,37°C),通过反相HPLC测定,培养的内皮细胞没有进一步通过ω -氧化转化这些化合物。这些数据表明,脂毒素可以刺激人内皮细胞生成pgi2。此外,它们表明花生四烯酸脂氧合酶产物在止血、炎症和血管反应性调节中的作用。
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 C4or 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‐PGF1α. Of the lipoxins examined, 7‐cis, 11‐trans‐lipoxin A4proved to be the most effective with PGI2production twice that induced by equimolar amounts of A‐23,187 (5 μM). On a molar basis, lipoxin A4and lipoxin B4were less potent than leukotriene C4although they were more efficacious. When either lipoxin A4or lipoxin B4was added to cells simultaneously with leukotriene C4, the formation of prostacyclin was greater than that induced by leukotriene C4alone. 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 PGI2generation 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.