Persoons J H, Schornagel K, Tilders F F, De Vente J, Berkenbosch F, Kraal G
Department of Cell Biology and Immunology, Vrije Universiteit, Amsterdam, The Netherlands.
Am J Respir Cell Mol Biol. 1996 Mar;14(3):272-8. doi: 10.1165/ajrcmb.14.3.8845178.
The effect of nitric oxide on the lipopolysaccharide (LPS)-induced cytokine production by alveolar macrophages was studied. When alveolar macrophages were cultured, substantial amounts of interleukin-1(IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha(TNF-alpha), and nitric oxide are produced upon stimulation with LPS. Inhibition of the nitric oxide production by the L-arginine analogue N(G)-monomethyl-L-arginine (NMMA), resulted in an increase of IL-1(beta) and IL-6, whereas the TNF-alpha concentrations remained unchanged, suggesting specific inhibitory effects of nitric oxide on the LPS-stimulated cytokine production by alveolar macrophages. The observed cytokine-modulation properties of nitric oxide did not result from cytotoxic actions of the oxidation of L-arginine on macrophages, since nitric oxide synthesis did not affect the viability of the alveolar macrophages. Conversely the nitric oxide donor S-nitroso-N-acetyl-D, L-penicillamine (SNAP) induced dose-dependent inhibition of IL-1 production in LPS-stimulated alveolar macrophages in which endogenous nitric oxide production was blocked. The results indicate that nitric oxide can affect the LPS-induced IL-1beta and IL-6 secretion by alveolar macrophages in an autoregulatory way and are discussed in view of the important physiologic consequences this autoregulation by nitric acid oxide may have.
研究了一氧化氮对脂多糖（LPS）诱导的肺泡巨噬细胞细胞因子产生的影响。培养肺泡巨噬细胞时，用LPS刺激后会产生大量白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、肿瘤坏死因子α（TNF-α）和一氧化氮。L-精氨酸类似物N（G）-单甲基-L-精氨酸（NMMA）抑制一氧化氮产生后，IL-1（β）和IL-6增加，而TNF-α浓度不变，提示一氧化氮对LPS刺激的肺泡巨噬细胞细胞因子产生具有特异性抑制作用。一氧化氮观察到的细胞因子调节特性并非L-精氨酸氧化对巨噬细胞的细胞毒性作用所致，因为一氧化氮合成不影响肺泡巨噬细胞的活力。相反，在阻断内源性一氧化氮产生的LPS刺激的肺泡巨噬细胞中，一氧化氮供体S-亚硝基-N-乙酰-D，L-青霉胺（SNAP）诱导了IL-1产生的剂量依赖性抑制。结果表明，一氧化氮可通过自调节方式影响LPS诱导的肺泡巨噬细胞IL-1β和IL-6分泌，并鉴于一氧化氮这种自调节可能产生的重要生理后果进行了讨论。
