Jones K L, Bryan T W, Jinkins P A, Simpson K L, Grisham M B, Owens M W, Milligan S A, Markewitz B A, Robbins R A
Departments of Medicine and Physiology and Biophysics, Overton Brooks Veterans Affairs and Louisiana State University Medical Centers, Shreveport, Louisiana 71101, USA.
Am J Physiol. 1998 Dec;275(6):L1120-6. doi: 10.1152/ajplung.1998.275.6.L1120.
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 (O-2) to form peroxynitrite, which can decompose into nitrate. Activated polymorphonuclear neutrophils (PMNs) releasing O-2 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 O-2 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 O-2 released from PMNs can decrease NO by conversion to nitrate and suggest a potential mechanism for modulation of NO levels in vivo.
呼出一氧化氮（NO）在某些炎症性气道疾病中会升高，但在诸如囊性纤维化和急性呼吸窘迫综合征等其他疾病中则不会。NO可与超氧化物（O₂⁻）结合形成过氧亚硝酸盐，而过氧亚硝酸盐可分解为硝酸盐。在诸如囊性纤维化等疾病中，释放O₂⁻的活化多形核中性粒细胞（PMN）可能是呼出NO减少的原因。为了在体外验证这一假设，我们刺激了小鼠肺上皮细胞系LA - 4细胞的汇合培养物以产生NO。随后，将被刺激产生O₂⁻的人PMN添加到LA - 4细胞中。观察到培养物上方顶空中NO逐渐增加，而添加PMN后其明显减少。测量了培养上清液中硝酸盐的增加，但未检测到亚硝酸盐增加。超氧化物歧化酶减弱了PMN的作用，黄嘌呤/黄嘌呤氧化酶重现了该作用。未观察到上皮细胞诱导型NO合酶蛋白或mRNA的变化。这些数据表明，PMN释放的O₂⁻可通过转化为硝酸盐来降低NO，并提示了体内调节NO水平的潜在机制。
