title: Nitrite attenuated peroxynitrite and hypochlorite generation in activated neutrophils.
abstract: Oxidative stress is usually considered as an important factor to the pathogenesis of various diseases. Peroxynitrite (ONOO(-)) and hypochlorite (OCl(-)) are formed in immune cells as a part of the innate host defense system, but excessive reactive oxygen species generation can cause progressive inflammation and tissue damage. It has been proven that through mediating nitric oxide (NO) homeostasis, inorganic nitrite (NO2(-)) shows organ-protective effects on oxidative stress and inflammation. However, the effects of NO2(-) on the function of immune cells were still not clear. The potential role of NO2(-) in modulating ONOO(-) and OCl(-) generation in neutrophil cells was investigated in this study. As an immune cell activator, lipopolysaccharide (LPS) increased both ONOO(-) and OCl(-) production in neutrophils, which was significantly attenuated by NO2(-). NO2(-) reduced superoxide (O2(·-)) generation via a NO-dependent mechanism and increased NO formation in activated neutrophils, suggesting a crucial role of O2(·-) in NO2(-)-mediated reduction of ONOO(-). Moreover, the reduced effect of NO2(-) on OCl(-) production was attributed to that NO2(-) reduced H2O2 production in activated neutrophils without influencing the release of myeloperoxidase (MPO), thus limiting OCl(-) production by MPO/H2O2 system. Therefore, NO2(-) attenuates ONOO(-) and OCl(-) formation in activated neutrophils, opening a new direction to modulate the inflammatory response.
authors: Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, Faculty of Materials Science and Engineering, Hubei University, Wuhan, China.
authors: Xiaoming
authors: X
authors: Ren
authors: Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, China.
authors: Yun
authors: Y
authors: Ding
authors: Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, China. Electronic address: naihaolu@jxnu.edu.cn.
authors: Naihao
authors: N
authors: Lu
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism*; D008070:Lipopolysaccharides; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D009573:Nitrites; D030421:Peroxynitrous Acid; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D014969:Xanthine Oxidase; D019255:NADPH Oxidases
keywords: Hypochlorite; Neutrophils activation; Nitrite; Peroxynitrite; Superoxide