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富含胆固醇的中性粒细胞产生大量一氧化氮样血管平滑肌舒张剂的证据。

Evidence for generation of a large amount of nitric oxide-like vascular smooth muscle relaxant by cholesterol-rich neutrophils.

作者信息

Mehta J L, Lawson D L, Nicolini F A, Cain D A, Mehta P, Schreier H

机构信息

Department of Medicine, University of Florida College of Medicine, Gainesville.

出版信息

Biochem Biophys Res Commun. 1990 Nov 30;173(1):438-42. doi: 10.1016/s0006-291x(05)81077-0.

DOI:10.1016/s0006-291x(05)81077-0
PMID:2175184
Abstract

To determine the effect of cholesterol incorporation on the ability of neutrophils to generate superoxide radicals and nitric oxide-like vasorelaxant material, isolated human neutrophils were incubated with cholesterol-rich liposomes, which increased total cholesterol content by 141% and esterified cholesterol content by 523%. Cholesterol loading resulted in 5 to 7 fold increase in cytosolic calcium in resting as well as in PMA or f-MLP-stimulated cells, but a marked (P less than 0.01) reduction in both PMA- and f-MLP-stimulated superoxide radical generation by these cells. Nitric oxide-like activity measured as relaxation of rat aortic rings was more pronounced (P less than 0.02) in cholesterol-rich than in cholesterol-poor cells. The greater relaxation of aortic rings in response to cholesterol-rich neutrophils was observed in rings with or without intact endothelium, and was potentiated by superoxide dismutase and inhibited by oxyhemoglobin as well as L-NMMA, thus suggesting that the vasorelaxant material was nitric oxide. The greater generation of nitric oxide by cholesterol-rich neutrophils occurs perhaps in response to increased cytosolic calcium.

摘要

为了确定胆固醇掺入对中性粒细胞产生超氧自由基和一氧化氮样血管舒张物质能力的影响,将分离的人中性粒细胞与富含胆固醇的脂质体一起孵育,这使得总胆固醇含量增加了141%,酯化胆固醇含量增加了523%。胆固醇加载导致静息以及经佛波酯(PMA)或N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸(f-MLP)刺激的细胞中胞质钙增加5至7倍,但这些细胞经PMA和f-MLP刺激产生的超氧自由基显著减少(P<0.01)。以大鼠主动脉环舒张来衡量的一氧化氮样活性,在富含胆固醇的细胞中比在胆固醇含量低的细胞中更明显(P<0.02)。在有或没有完整内皮的主动脉环中,均观察到富含胆固醇的中性粒细胞引起的主动脉环舒张更明显,并且超氧化物歧化酶可增强这种舒张,而氧合血红蛋白以及L- NAME(N-甲基-L-精氨酸)可抑制这种舒张,因此表明血管舒张物质是一氧化氮。富含胆固醇的中性粒细胞产生更多一氧化氮可能是对胞质钙增加的反应。

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