Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils

• Published in: Nature (London) 1998-01, Vol.391 (6665), p.393-397
• Main Authors: Eiserich, Jason P, Hristova, Milena, Cross, Carroll E, Jones, A. Daniel, Freeman, Bruce A, Halliwell, Barry, van der Vliet, Albert
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biocompatibility; Biological and medical sciences; Biomedical materials; Cattle; Chlorides - metabolism; Chlorination; Endothelium, Vascular - metabolism; Enzymes; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Humans; Hypochlorous Acid - metabolism; In Vitro Techniques; Inactivation; Inflammation; Inflammation Mediators - metabolism; letter; Metabolism; Molecular and cellular biology; multidisciplinary; Neutrophils - enzymology; Neutrophils - immunology; Neutrophils - metabolism; Nitration; Nitric oxide; Nitric Oxide - metabolism; Nitrites - metabolism; Nitrogen dioxide; Oxidants; Oxidants - metabolism; Oxidation; Oxidizing agents; Peroxidase - metabolism; Phenols; Science; Science (multidisciplinary); Surgical implants; Tyrosine
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/34923

Nitric oxide ( NO) plays a central role in the pathogenesis of diverse inflammatory and infectious disorders,. The toxicity of NO is thought to be engendered, in part, by its reaction with superoxide (O −2), yielding the potent oxidant peroxynitrite (ONOO−). However, evidence for a role of ONOO− in vivo is based largely upon detection of 3-nitrotyrosine in injured tissues. We have recently demonstrated that nitrite (NO2−), a major end-product of NO metabolism, readily promotes tyrosine nitration through formation of nitryl chloride (NO2Cl) and nitrogen dioxide ( NO2) by reaction with the inflammatory mediators hypochlorous acid (HOCl) or myeloperoxidase,. We now show that activated human polymorphonuclear neutrophils convert NO2− into NO2Cl and NO2 through myeloperoxidase-dependent pathways. Polymorphonuclear neutrophil-mediated nitration and chlorination of tyrosine residues or 4-hydroxyphenylacetic acid is enhanced by addition of NO2− or by fluxes of NO. Addition of 15NO2− led to 15N enrichment of nitrated phenolic substrates, confirming its role in polymorphonuclear neutrophil-mediated nitration reactions. Polymorphonuclear neutrophil-mediated inactivation of endothelial cell angiotensin-converting enzyme was exacerbated by NO2−, illustrating the physiological significance of these reaction pathways to cellular dysfunction. Our data reveal that NO2− may regulate inflammatory processes through oxidative mechanisms, perhaps by contributing to the tyrosine nitration and chlorination observed in vivo.