Nitrolinoleate inhibits superoxide generation, degranulation, and integrin expression by human neutrophils: novel antiinflammatory properties of nitric oxide-derived reactive species in vascular cells

Coles, Barbara, Bloodsworth, Allison, Clark, Stephen Robert ORCID: https://orcid.org/0000-0001-5907-9671, Lewis, Malcolm John, Cross, Andrew R., Freeman, Bruce A. and O'Donnell, Valerie Bridget ORCID: https://orcid.org/0000-0003-4089-8460 2002. Nitrolinoleate inhibits superoxide generation, degranulation, and integrin expression by human neutrophils: novel antiinflammatory properties of nitric oxide-derived reactive species in vascular cells. Circulation Research 91 (5) , pp. 375-381. 10.1161/01.RES.0000032114.68919.EF

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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, LNO2 was observed to inhibit human neutrophil function. LNO2, but not linoleic acid or the nitrated amino acid 3-nitrotyrosine, dose-dependently (0.2 to 1 µmol/L) inhibited superoxide (O2·-) generation, Ca2+ influx, elastase release, and CD11b expression in response to either phorbol 12-myristate 13-acetate or N-formyl-Met-Leu-Phe. LNO2 did 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, LNO2 caused 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 LNO2 may inhibit signaling both upstream and downstream of protein kinase C. These data suggest novel signaling actions for LNO2 in 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Uncontrolled Keywords:	Nitric oxide ; Nitrolinoleate ; Neutrophils ; Atherosclerosis ; Peroxynitrite
Additional Information:	Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0009-7330/ (accessed 19/02/2014).
Publisher:	American Heart Association
ISSN:	0009-7330
Related URLs:	http://www.ncbi.nlm.nih.gov/entrez/query...
Date of First Compliant Deposit:	30 March 2016
Last Modified:	31 Jan 2025 22:22
URI:	https://orca.cardiff.ac.uk/id/eprint/20

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