Mauël J
Bull Eur Physiopathol Respir. 1983 Mar-Apr;19(2):115-22.
The understanding of mechanisms whereby phagocytic cells destroy intracellular microorganisms has progressed considerably in recent years. The interaction of phagocytes with microbes starts with binding of the latter to the phagocyte. This binding can be mediated by opsonins on the microorganisms, which then interact with appropriate receptors on the phagocyte surface. Other types of receptors, such as lectins, may also be involved in this process. Following internalization, the microbe will be enclosed in a vesicle (the phagosome), whose membrane is derived from the plasma membrane of the phagocytic cell. The phagosome will then normally undergo fusion with primary or secondary lysosomes. Various mechanisms can then lead to intracellular killing; some depend on oxidative processes, whereas other are independent of the oxidative metabolism. The former involve the activation of membrane enzyme systems that lead to a stimulation of oxygen uptake (the "respiratory burst"), and its reduction to molecular species that are highly toxic for microorganisms. Differences appear to exist in this regard between alveolar macrophages and other phagocytes, in which the respiratory burst is of higher magnitude. Oxygen-independent microbicidal mechanisms are based on the production of acid, on the secretion of lysozyme, on iron-binding proteins, and on the synthesis of toxic cationic polypeptides. Both oxygen-dependent and independent mechanisms appear to be increased in activated macrophages. Certain microorganisms have evolved countermeasures which enable them to avoid being destroyed by phagocytes; these are well illustrated by studies of the interaction between macrophages and protozoan parasites. Parasites such as Toxoplasma gondii (as well as certain mycobacteria) are able to inhibit fusion of phagosomes with lysosomes, thus escaping from the potentially harmful action of lysosomal hydrolases. Other microorganisms are able to resist the effect of such enzymes, perhaps by secreting inhibitory substances. Other still avoid lysosomes by leaving the phagocytic vacuole, to reach the cytosolic matrix where their development is unhindered. Finally, some microbes have enzymes to detoxify oxygen metabolites formed during the respiratory burst. Intracellular death or survival will thus depend on a delicate balance between several factors, some of which appear to be under genetic control.
近年来，对吞噬细胞破坏细胞内微生物机制的理解有了显著进展。吞噬细胞与微生物的相互作用始于微生物与吞噬细胞的结合。这种结合可由微生物上的调理素介导，调理素随后与吞噬细胞表面的相应受体相互作用。其他类型的受体，如凝集素，也可能参与这一过程。内化后，微生物将被包裹在一个囊泡（吞噬体）中，其膜来源于吞噬细胞的质膜。吞噬体随后通常会与初级或次级溶酶体融合。然后，各种机制可导致细胞内杀伤；有些依赖于氧化过程，而其他则与氧化代谢无关。前者涉及膜酶系统的激活，这会导致氧气摄取的刺激（“呼吸爆发”），并将其还原为对微生物剧毒的分子形式。在这方面，肺泡巨噬细胞和其他吞噬细胞似乎存在差异，其中呼吸爆发的程度更高。不依赖氧气的杀菌机制基于酸的产生、溶菌酶的分泌、铁结合蛋白以及有毒阳离子多肽的合成。在活化的巨噬细胞中，依赖氧气和不依赖氧气的机制似乎都有所增强。某些微生物已经进化出应对措施，使它们能够避免被吞噬细胞破坏；巨噬细胞与原生动物寄生虫之间相互作用的研究很好地说明了这一点。诸如刚地弓形虫（以及某些分枝杆菌）等寄生虫能够抑制吞噬体与溶酶体的融合，从而逃避溶酶体水解酶的潜在有害作用。其他微生物能够抵抗此类酶的作用，可能是通过分泌抑制性物质。还有一些微生物通过离开吞噬泡来避开溶酶体，到达细胞质基质，在那里它们的发育不受阻碍。最后，一些微生物具有酶来解毒呼吸爆发过程中形成的氧代谢产物。因此，细胞内的死亡或存活将取决于几个因素之间的微妙平衡，其中一些因素似乎受遗传控制。
