Effector molecules in expression of the antimicrobial activity of macrophages against Mycobacterium avium complex: roles of reactive nitrogen intermediates, reactive oxygen intermediates, and free fatty acids
Effector molecules in expression of the antimicrobial activity of macrophages against Mycobacterium avium complex: roles of reactive nitrogen intermediates, reactive oxygen intermediates, and free fatty acids
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DOI：
10.1002/jlb.62.6.795
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发表时间：
1997-12-01
影响因子：
5.5
通讯作者：
Tomioka, H
中科院分区：
文献类型：
--
作者：
Akaki, T;Sato, K;Tomioka, H
我们研究了活性氮中间体 (RNI)、游离脂肪酸 (FEA) 和活性氧中间体 (ROI) 对鸟分枝杆菌复合体 (MAC) 的杀菌活性以及这些效应物的巨噬细胞 (m phi) 产生模式，(1) ROI 或 RNI 清除剂以及一氧化氮合酶或磷脂酶 A 抑制剂加速了小鼠腹膜 m phi 中 MAC 的细胞内生长(2)，表明ROI、RNI和FFA在m phi抗MAC功能中的作用，（2）酸化NaNO2衍生的RNI、FFA（亚麻酸和花生四烯酸）和H2O2介导的卤化系统表现出显着的抗MAC杀菌活性，RNI与FFA组合显示出协同作用，然而，H2O2-卤化系统与RNI或FFA组合显示出拮抗作用，当李斯特菌时以单核细胞增生李斯特菌（Lm）为靶标生物，RNI+FFA和RNI+H2O2-卤化的组合具有协同作用，而FFA+H2O2-卤化在发挥杀菌活性方面表现出拮抗作用。此外，当黄嘌呤氧化酶-乙醛系统产生的ROI与RNI组合时，增强了抗lm活性，但不增强抗MAC活性。（3）ROI产生与MAC生物体（MAC刺激）接触后立即观察到小鼠腹膜mphis并在2小时内停止，在MAC刺激后1-24小时观察到FFA释放，RNI产生从3小时开始并在前36小时内增加并持续至少4天，这些发现表明RNI和FFA而不是ROI是mphis抗MAC功能的重要影响者，并且RNI与FEA的协同作用暂时参与了mphis的抗MAC功能。 m phi 在 MAC 刺激后相对早期阶段介导的 MAC 杀伤。
We studied microbicidal activities of reactive nitrogen intermediates (RNI), free fatty acids (FEA), and reactive oxygen intermediates (ROI) against Mycobacterium avium complex (MAC) and the mode of macrophage (m phi) production of these effecters, (1) Intracellular growth of MAC in murine peritoneal m phi s was accelerated by scavengers for ROI or RNI and inhibitors of nitric oxide synthase or phospholipase A(2), indicating roles of ROI, RNI, and FFA in m phi anti-MAC functions, (2) Acidified NaNO2-derived RNI, FFA (linolenic and arachidonic acids), and the H2O2-mediated halogenation system exhibited a significant anti-MAC bactericidal activity, The combination of RNI with FFA showed a synergistic effect, However, the H2O2-halogenation system in combination with either RNI or FFA showed an antagonism, When Listeria monocytogenes (Lm) was used as a target organism, the combinations of RNI + FFA and RNI + H2O2-halogenation gave a synergistic effect, whereas FFA + H2O2-halogenation showed an antagonism in exerting bactericidal activity, In addition, when ROI generated by the xanthine oxidase-acetaldehyde system was combined with RNI, anti-lm but not anti-MAC activity was potentiated, (3) ROI production by murine peritoneal m phi s was observed immediately after contact with MAC organisms (MAC stimulation) and ceased within 2 h, FFA release was seen 1-24 h after MAC stimulation, RNI production was initiated from 3 h and increased during the first 36 h and continued at least for 4 days, These findings suggest that RNI and FFA rather than ROI are important effecters of anti-MAC functions of m phi s, and the collaborating action of RNI with FEA temporarily participates in m phi-mediated killing of MAC in the relatively early phase after MAC stimulation.