Liew F Y
Department of Immunology, University of Glasgow, U.K.
Ann Trop Med Parasitol. 1993 Dec;87(6):637-42. doi: 10.1080/00034983.1993.11812822.
Murine macrophages express high levels of nitric oxide synthase and produce large amounts of nitric oxide (NO) when stimulated with certain cytokines in the presence of a trace amount of lipopolysaccharide (LPS). The stimulatory cytokines include interleukin-1 (IL-1), interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and migration inhibitory factor. Activated macrophages are highly effective killers of intra- and extra-cellular pathogens. However, as excessive NO can lead to immunopathology (diabetes, graft-v.-host disease, EAE, liver cirrhosis, rheumatoid arthritis), NO production is necessarily under tight regulation. A number of cytokines, including IL-4, IL-10 and transforming growth factor-beta, can down regulate the induction of NO synthase in macrophages. In addition, macrophages exposed to LPS alone and then stimulated with a mix of IFN-gamma and LPS express significantly lower levels of NO synthase than cells stimulated without pre-exposure to LPS. Furthermore, NO can reduce the activity of NO synthase by feedback inhibition, and also inhibit the production of IFN-gamma by Th1 cells (thus turning off its own synthesis from upstream). The regulatory pathways involve tyrosine kinase and protein kinase C.
在微量脂多糖（LPS）存在的情况下，用某些细胞因子刺激时，小鼠巨噬细胞会表达高水平的一氧化氮合酶并产生大量一氧化氮（NO）。刺激细胞因子包括白细胞介素-1（IL-1）、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）和迁移抑制因子。活化的巨噬细胞是细胞内和细胞外病原体的高效杀手。然而，由于过量的NO会导致免疫病理学（糖尿病、移植物抗宿主病、实验性自身免疫性脑脊髓炎、肝硬化、类风湿性关节炎），因此NO的产生必然受到严格调控。包括IL-4、IL-10和转化生长因子-β在内的多种细胞因子可下调巨噬细胞中一氧化氮合酶的诱导。此外，仅暴露于LPS然后用IFN-γ和LPS混合物刺激的巨噬细胞，其一氧化氮合酶的表达水平明显低于未预先暴露于LPS而刺激的细胞。此外，NO可通过反馈抑制降低一氧化氮合酶的活性，还可抑制Th1细胞产生IFN-γ（从而从上游关闭其自身的合成）。调节途径涉及酪氨酸激酶和蛋白激酶C。
