Superoxide released from neutrophils causes a reduction in nitric oxide gas

Autor: Matthew B. Grisham, Keith Simpson, Ty W. Bryan, Patricia A. Jinkins, Michael W. Owens, Shawn A. Milligan, Richard A. Robbins, Kimberly L. Jones, Boaz A. Markewitz
Rok vydání: 1998
Předmět:
Zdroj: American Journal of Physiology-Lung Cellular and Molecular Physiology. 275:L1120-L1126
ISSN: 1522-1504
1040-0605
DOI: 10.1152/ajplung.1998.275.6.l1120
Popis: Exhaled nitric oxide (NO) is increased in some inflammatory airway disorders but not in others such as cystic fibrosis and acute respiratory distress syndrome. NO can combine with superoxide ([Formula: see text]) to form peroxynitrite, which can decompose into nitrate. Activated polymorphonuclear neutrophils (PMNs) releasing[Formula: see text] could account for a reduction in exhaled NO in disorders such as cystic fibrosis. To test this hypothesis in vitro, we stimulated confluent cultures of LA-4 cells, a murine lung epithelial cell line, to produce NO. Subsequently, human PMNs stimulated to produce [Formula: see text] were added to the LA-4 cells. A gradual increase in NO in the headspace above the cultures was observed and was markedly reduced by the addition of PMNs. An increase in nitrate in the culture supernatant fluids was measured, but no increase in nitrite was detected. Superoxide dismutase attenuated the PMN effect, and xanthine/xanthine oxidase reproduced the effect. No changes in epithelial cell inducible NO synthase protein or mRNA were observed. These data demonstrate that [Formula: see text]released from PMNs can decrease NO by conversion to nitrate and suggest a potential mechanism for modulation of NO levels in vivo.
Databáze: OpenAIRE