Corriveau C C, Madara P J, Van Dervort A L, Tropea M M, Wesley R A, Danner R L
Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Infect Dis. 1998 Jan;177(1):116-26. doi: 10.1086/513829.
The effects of nitric oxide (NO) on human neutrophil chemotactic responses and release of interleukin (IL)-8 was studied. Neutrophils exposed to chemoattractants (IL-8, FMLP, leukotriene B4, and C5a) failed to show increases in intracellular guanosine 3',5'-cyclic monophosphate (cGMP), an indicator of NO production. Although NO increased cGMP in neutrophils, neither of two NO donors (sodium nitroprusside and 3-morpholino-sydonimine) nor a NO synthase inhibitor (N omega-nitro-L-arginine) altered FMLP- or IL-8-elicited neutrophil chemotaxis (P > .25 for all). However, lipopolysaccharide-induced IL-8 production was increased in a dose-dependent manner by a combination of sodium nitroprusside and N-acetylcysteine (P = .03) or by S-nitrosoglutathione (P = .004). NO-augmented IL-8 release was not reproduced by treating neutrophils with dibutyryl-cGMP. Up-regulation of IL-8 release by NO was associated with increased IL-8 mRNA levels (P = .009). These data suggest that NO does not directly affect neutrophil chemotaxis but may indirectly alter chemotactic responses by increasing IL-8 production via a cGMP-independent pathway.
研究了一氧化氮（NO）对人中性粒细胞趋化反应及白细胞介素（IL）-8释放的影响。暴露于趋化因子（IL-8、N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）、白三烯B4和C5a）的中性粒细胞，细胞内鸟苷3',5'-环磷酸（cGMP）未显示增加，而cGMP是NO产生的一个指标。尽管NO可增加中性粒细胞内的cGMP，但两种NO供体（硝普钠和3-吗啉代-西多明）及一种NO合酶抑制剂（Nω-硝基-L-精氨酸）均未改变FMLP或IL-8诱导的中性粒细胞趋化性（所有P>.25）。然而，硝普钠与N-乙酰半胱氨酸联合使用（P=.03）或S-亚硝基谷胱甘肽（P=.004）可使脂多糖诱导的IL-8产生呈剂量依赖性增加。用二丁酰-cGMP处理中性粒细胞未重现NO增强的IL-8释放。NO上调IL-8释放与IL-8 mRNA水平增加相关（P=.009）。这些数据表明，NO不直接影响中性粒细胞趋化性，但可能通过cGMP非依赖途径增加IL-8产生而间接改变趋化反应。
