Superoxide released from neutrophils causes a reduction in nitric oxide gas

Abstract

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.

Nasal nitric oxide measurements for the screening of primary ciliary dyskinesia

“…Other authors have demonstrated high concentrations of the NO metabolites nitrate and nitrite in CF airway secretions. In vitro studies have shown that superoxide anion release from activated polymorphonuclear neutrophils reduces airway epithelial cell-derived NO by forming nitrate [31]. This suggests that airway NO in CF could be decreased by degradation in airway fluids and this needs to be investigated in PCD.…”

An increase in exhaled nitric oxide is not associated with activity in pulmonary sarcoidosis

“…This is the major route for elimination of peroxynitrite [26]. JONES et al [27] demonstrated that the superoxide generated by neutrophils causes a decrease in eNO concentration in patients with cystic fibrosis. It has been revealed that the consumption by superoxide of NO decreases from the large to the small airways.…”

Nitric oxide in primary ciliary dyskinesia

“…As nitric oxide is highly reactive, it is rapidly broken down from the breath exhalate by its reaction with, among others, oxygen, superoxides and cysteine thiols, producing reactive nitrogen species, including the potent oxidants peroxynitrite and nitrogen dioxide, and S-nitrosothiols [72][73][74][75].…”