Failure to trigger the oxidative metabolic burst by normal macrophages: possible mechanism for survival of intracellular pathogens
Failure to trigger the oxidative metabolic burst by normal macrophages: possible mechanism for survival of intracellular pathogens
复制标题
正常巨噬细胞未能触发氧化代谢爆发：细胞内病原体生存的可能机制
DOI：
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发表时间：
1980
影响因子：
15.3
通讯作者：
J. Remington
中科院分区：
文献类型：
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作者：
C. Wilson;V. Tsai;J. Remington
如前所述，正常人单核细胞（11）和活化的小鼠巨噬细胞（9）能够杀死或抑制未被抗体包被的弓形虫的细胞内复制，而正常人和小鼠巨噬细胞则不能（7，9）。这些类型的单核吞噬细胞都能够杀死抗体包被的弓形虫。在我们的研究中，吞噬抗体包被的弓形虫刺激呼吸爆发的每一种类型的单核吞噬细胞，而吞噬生物体，没有抗体包被刺激呼吸爆发，只有人单核细胞和激活的小鼠巨噬细胞。弓形虫的吞噬作用并不抑制正常巨噬细胞产生活性氧代谢产物，相反，它未能刺激其生产。X连锁慢性肉芽肿病患儿及其杂合子母亲的单核细胞对弓形虫的杀伤作用受损。因此，活性氧代谢产物，可能与溶酶体内容物一起，似乎是单核吞噬细胞杀死这种生物体的第一线机制。我们不能确定单核吞噬细胞抑制未被杀死的弓形虫复制的确切机制，尽管可能涉及氧依赖性和其他非溶酶体机制。我们观察到的氧化反应弓形虫的吞噬作用的差异似乎是这些细胞的抗菌活性的一个决定因素，并可能占一些细胞内的病原体的吞噬细胞内生存的能力。这些差异可能与膜有关。需要进一步研究弓形虫膜、弓形虫的吞噬细胞膜受体以及呼吸爆发激活的膜相关机制，以确定其真正的基础。
As previously reported, normal human monocytes (11) and activated mouse macrophages (9) are able to kill or inhibit intracellular replication of Toxoplasma that are not antibody coated, whereas normal human and mouse macrophages are not (7, 9). Each of these types of mononuclear phagocytes is able to kill antibody-coated Toxoplasma. In our studies, phagocytosis of antibody-coated Toxoplasma stimulated the respiratory burst by each of these types of mononuclear phagocytes, whereas phagocytosis of organisms that were not antibody coated stimulated the respiratory burst only by human monocytes and by activated mouse macrophages. Phagocytosis of Toxoplasma did not inhibit production of reactive oxygen metabolites by normal macrophages; rather, it failed to stimulate their production. Killing of Toxoplasma by monocytes from a child with X-linked chronic granulomatous disease and his heterozygote mother was impaired. Thus, reactive oxygen metabolites, perhaps in conjunction with lysosomal contents, appear to be first-line mechanisms whereby mononuclear phagocytes kill this organism. We were not able to determine the exact mechanisms whereby mononuclear phagocytes inhibit the replication of those Toxoplasma that were not killed, although both oxygen-dependent and other nonlysosomal mechanisms may be involved. The differences we observed in oxidative response to phagocytosis of Toxoplasma appear to be one determinant of the antimicrobial activity of these cells and may account for the ability of some intracellular pathogens to survive within phagocytes. These differences may be membrane related. Further studies of Toxoplasma membranes, phagocyte membrane receptors for Toxoplasma, and membrane-related mechanisms for activation of the respiratory burst are needed to define their true basis.