LIPOARABINOMANNAN, A POSSIBLE VIRULENCE FACTOR INVOLVED IN PERSISTENCE OF MYCOBACTERIUM-TUBERCULOSIS WITHIN MACROPHAGES
LIPOARABINOMANNAN, A POSSIBLE VIRULENCE FACTOR INVOLVED IN PERSISTENCE OF MYCOBACTERIUM-TUBERCULOSIS WITHIN MACROPHAGES
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DOI：
10.1128/iai.59.5.1755-1761.1991
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发表时间：
1991-05-01
影响因子：
3.1
通讯作者：
BLOOM, BR
中科院分区：
文献类型：
--
作者：
CHAN, J;FAN, X;BLOOM, BR
结核分枝杆菌和麻风分枝杆菌分别是结核病和麻风病的病原体，它们产生大量的脂阿拉伯甘露聚糖（LAM），一种高度免疫原性的细胞壁相关糖脂。 该分子先前已报道为γ干扰素介导的鼠巨噬细胞活化的有效抑制剂。 对这种分枝杆菌糖脂下调巨噬细胞效应子功能的机制的研究提供了证据，表明LAM在几个水平上起作用，并且它可以（i）抑制潜在的细胞毒性氧自由基，（ii）抑制蛋白激酶C活性，（iii）阻断人巨噬细胞样细胞系中γ干扰素诱导基因的转录激活。 这些结果表明，LAM可以抑制巨噬细胞的激活和触发和杀细胞活性，它可能是一种化学定义的毒力因子，有助于单核吞噬细胞内的分枝杆菌的持久性。
Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis and leprosy, respectively, produce large quantities of lipoarabinomannan (LAM), a highly immunogenic, cell wall-associated glycolipid. This molecule has been previously reported to be a potent inhibitor of gamma interferon-mediated activation of murine macrophages. Studies of the mechanism by which this mycobacterial glycolipid down-regulates macrophage effector functions provide evidence that LAM acts at several levels and that it can (i) scavenge potentially cytotoxic oxygen free radicals, (ii) inhibit protein kinase C activity, and (iii) block the transcriptional activation of gamma interferon-inducible genes in human macrophage-like cell lines. These results suggest that LAM can inhibit macrophage activation and triggering and cytocidal activity and that it may represent a chemically defined virulence factor contributing to the persistence of mycobacteria within mononuclear phagocytes.