Decreased exhaled nitric oxide as a marker of postinsult immune paralysis
Open Access
- 1 October 2004
- journal article
- Published by American Physiological Society in Journal of Applied Physiology
- Vol. 97 (4) , 1188-1194
- https://doi.org/10.1152/japplphysiol.00840.2003
Abstract
Nitric oxide (NO) regulates neutrophil migration and alveolar macrophage functions such as cytokine synthesis and bacterial killing, both of which are impaired in immune paralysis associated with critical illness. The aim of this study was to determine whether NO is involved in immune paralysis and whether exhaled NO measurement could help to monitor pulmonary defenses. NO production (protein expression, enzyme activity, end products, and exhaled NO measurements) was assessed in rats after cecal ligation and puncture to induce a mild peritonitis (leading to ∼20% mortality rate). An early and sustained decrease in exhaled NO was found after peritonitis (from 1 to 72 h) compared with healthy rats [median (25th–75th percentile), 1.5 parts per billion (ppb) (1.2–1.7) vs. 4.0 ppb (3.6–4.3), P < 0.05], despite increased NO synthase-2 and unchanged NO synthase-3 protein expression in lung tissue. NO synthase-2 activity was decreased in lung tissue. Nitrites and nitrates in supernatants of isolated alveolar macrophages decreased after peritonitis compared with healthy rats, and an inhibitory experiment suggested arginase overactivity in alveolar macrophages bypassing the NO substrate. Administration of the NO synthase-2 inhibitor aminoguanidine to healthy animals reproduced the decreased neutrophil migration toward alveolar spaces that was observed after peritonitis, but l-arginine administration after peritonitis failed to correct the defect of neutrophil emigration despite increasing exhaled NO compared with d-arginine administration [4.8 (3.9–5.7) vs. 1.6 (1.3–1.7) ppb, respectively, P < 0.05]. In conclusion, the decrease in exhaled NO observed after mild peritonitis could serve as a marker for lung immunodepression.Keywords
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