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Nitrolinoleate Inhibits Superoxide Generation, Degranulation, and Integrin Expression b...
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Nitrolinoleate Inhibits Superoxide Generation, Degranulation, and Integrin Expression by Human NeutrophilsNovel Antiinflammatory Properties of Nitric Oxide-Derived Reactive Species in Vascular Cells
作者:
Barbara Coles,
Allison Bloodsworth,
Stephen Clark,
Malcolm Lewis,
Andrew Cross,
Bruce Freeman,
Valerie O’Donnell,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2002)
卷期:
Volume 91,
issue 5
页码: 375-381
ISSN:0009-7330
年代: 2002
出版商: OVID
关键词: nitric oxide;nitrolinoleate;neutrophils;atherosclerosis;peroxynitrite
数据来源: OVID
摘要:
Abstract—Nitration of unsaturated fatty acids such as linoleate by NO-derived reactive species forms novel derivatives (including nitrolinoleate [LNO2]) that can stimulate smooth muscle relaxation and block platelet activation by either NO/cGMP or cAMP-dependent mechanisms. Here, LNO2was observed to inhibit human neutrophil function. LNO2, but not linoleic acid or the nitrated amino acid 3-nitrotyrosine, dose-dependently (0.2 to 1 &mgr;mol/L) inhibited superoxide (O2·−) generation, Ca2+influx, elastase release, and CD11b expression in response to either phorbol 12-myristate 13-acetate orN-formyl-Met-Leu-Phe. LNO2did not elevate cGMP, and inhibition of guanylate cyclase by 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one did not restore neutrophil responses, ruling out a role for NO. In contrast, LNO2caused elevations in intracellular cAMP in the presence and absence of phosphodiesterase inhibition, suggesting activation of adenylate cyclase. Compared with phorbol 12-myristate 13-acetate–activated neutrophils,N-formyl-Met-Leu-Phe–activated neutrophils were more susceptible to the inhibitory effects of LNO2, indicating that LNO2may inhibit signaling both upstream and downstream of protein kinase C. These data suggest novel signaling actions for LNO2in mediating its potent inhibitory actions. Thus, nitration of lipids by NO-derived reactive species yields products with antiinflammatory properties, revealing a novel mechanism by which NO-derived nitrated biomolecules can influence the progression of vascular disease.
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