Oswald I P, Wynn T A, Sher A, James S L
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Comp Biochem Physiol Pharmacol Toxicol Endocrinol. 1994 May;108(1):11-8. doi: 10.1016/1367-8280(94)90083-3.
It has recently been appreciated that NO, a molecule previously known to play a physiologic role in blood pressure regulation, is a major effector molecule of macrophage cytotoxicity against a variety of microbial targets, including protozoan and helminth parasites. NO production by macrophages is arginine dependent and catalyzed by a cytokine-inducible form of the NO synthase. This activity is positively controlled by several up-regulatory stimuli (including IFN-gamma, TNF-alpha, IL-2) and negatively controlled by others (principally IL-10, IL-4, TGF-beta). Other cell types, such as endothelial cells and hepatocytes, display a similar capacity for NO production in response to cytokine stimulation. In murine models of leishmaniasis and schistosomiasis, in vivo NO synthesis correlates with protective immunity against infection. The effector molecule that plays a similar role in cell-mediated immunity in man has not yet been identified.
最近人们认识到，一氧化氮（NO）这种先前已知在血压调节中发挥生理作用的分子，是巨噬细胞对多种微生物靶点（包括原生动物和蠕虫寄生虫）产生细胞毒性的主要效应分子。巨噬细胞产生NO依赖于精氨酸，并由细胞因子诱导型一氧化氮合酶催化。这种活性受到几种上调刺激（包括干扰素-γ、肿瘤坏死因子-α、白细胞介素-2）的正向调控，而受到其他刺激（主要是白细胞介素-10、白细胞介素-4、转化生长因子-β）的负向调控。其他细胞类型，如内皮细胞和肝细胞，在受到细胞因子刺激时也表现出类似的产生NO的能力。在利什曼病和血吸虫病的小鼠模型中，体内NO合成与对感染的保护性免疫相关。在人类细胞介导的免疫中发挥类似作用的效应分子尚未确定。
