Author
Listed:
- Jason P. Eiserich
(University of California
The University of Alabama at Birmingham)
- Milena Hristova
(University of California)
- Carroll E. Cross
(University of California)
- A. Daniel Jones
(Facility for Advanced Instrumentation, University of California)
- Bruce A. Freeman
(Biochemistry and Molecular Genetics, Pediatrics, and the UAB Center for Free Radical Biology, University of Alabama at Birmingham)
- Barry Halliwell
(University of California
Neurodegenerative Disease Research Centre, Pharmacology Group, University of London, King's College)
- Albert van der Vliet
(University of California)
Abstract
Nitric oxide (˙NO) plays a central role in the pathogenesis of diverse inflammatory and infectious disorders1,2. The toxicity of ˙NO is thought to be engendered, in part, by its reaction with superoxide (O˙−2), yielding the potent oxidant peroxynitrite (ONOO−)3. However, evidence for a role of ONOO− in vivo is based largely upon detection of 3-nitrotyrosine in injured tissues4,5,6,7,8. 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 myeloperoxidase9,10. 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.
Suggested Citation
Jason P. Eiserich & Milena Hristova & Carroll E. Cross & A. Daniel Jones & Bruce A. Freeman & Barry Halliwell & Albert van der Vliet, 1998.
"Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils,"
Nature, Nature, vol. 391(6665), pages 393-397, January.
Handle:
RePEc:nat:nature:v:391:y:1998:i:6665:d:10.1038_34923
DOI: 10.1038/34923
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