THE RESPIRATORY BURST OF PHAGOCYTES
THE RESPIRATORY BURST OF PHAGOCYTES
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DOI：
10.1172/jci111249
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发表时间：
1984-01-01
影响因子：
15.9
通讯作者：
BABIOR, BM
中科院分区：
文献类型：
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作者：
BABIOR, BM
通过一种以上的途径发生，因为根据刺激，它与滞后有关或无关（19），需要或不需要外源性钙（20），并且伴随或不伴随胞质钙的增加或释放到胞质中的知之甚少的”膜结合钙库”（21-23）。从这些混乱的发现中，除了激活氧化酶的生化途径是多方面的和复杂的之外，几乎没有得出什么结论，这并不奇怪;另一方面，在各种类型的细胞暴露于外部刺激时，已经看到了许多生化事件的发生，其中一些可能为呼吸爆发激活的分子基础提供线索。例如，Nishizuka及其同事已经证明，强有力的呼吸爆发激活剂佛波醇肉豆蔻酸酯结合并激活一种膜相关的磷酸化酶，称为蛋白激酶C（24），这增加了一种可能性（正在寻找，但尚未发现），即氧化酶的激活可能是激活蛋白磷酸化状态变化的结果。在许多种细胞中，由刺激诱导的膜磷脂的快速和广泛的变化（25-27）表明了氧化酶可能被激活的其他生化机制。在无细胞系统的研究中，还出现了其他改变活性的方法：3-Fe和4-Fe铁硫中心之间的相互转化（28），精氨酸残基的ADP核糖基化（29），催化和调节亚基之间的复合物形成（30）只是几个例子。然而，这些生化激活机制与呼吸爆发的发生之间的明确联系尚未建立。当应用于仅涉及单核吞噬细胞的吞噬细胞时，术语”活化”有第二种含义。在第二种意义上，“活化”是指一系列导致破坏力普遍增加的变化，这些破坏力是通过暴露于内毒素或淋巴因子γ-干扰素在这些细胞中引起的。这些变化包括最大刺激吞噬细胞呼吸爆发活动的改变。这些变化在驻留的腹腔巨噬细胞中最为明显，它们在新鲜分离时几乎没有呼吸爆发，但在合适的活化剂存在下培养2或3天后获得了大量的制造O2的能力（31），只是在进一步培养时失去了这种能力（32）。这第二种形式的激活机制很少受到关注;在所有的可能性中，它将涉及由激活剂诱导的基因表达的重大变化。
occur by more than one route, since depending upon the stim-ulus, it is or is not associated with a lag (19), does or does not require exogenous calcium (20), and is or is not accompanied by an increase in cytosolic calcium or the release into the cy-toplasm of a poorly understood" membrane-bound calcium pool"(21-23). It is not surprising that little has been concluded from this confusing welter of findings beyond the idea that biochemical pathways for activating the oxidase are multiple and complex.On the other hand, a number of biochemical events have been seen to occur on exposure of various types of cells to external stimuli, and some of these may provide clues to the molecular basis for respiratory burst activation. Nishizuka and associates, for instance, have shown that the powerful respiratory burst activator, phorbol myristate acetate, binds and activates a membrane-associated phosphorylating enzyme known as pro-tein kinase C (24), raising the possibility (sought but not yet found) that the activation of the oxidase might be the consequence ofa change in the state ofphosphorylation ofan activator protein. Rapid and extensive alterations in membrane phos-pholipids which are induced by stimulation in many kinds of cells (25-27) suggest additional biochemical mechanisms by which the oxidase might be activated. Still other ways to vary activity have emerged from studies with cell-free systems: in-terconversion between 3-Fe and 4-Fe iron-sulfur centers (28), ADP-ribosylation of arginine residues (29), and complex formation between catalytic and regulatory subunits (30) are only a few examples. A clearconnection, however, between any of these biochemical activating mechanisms and the onset of the respiratory burst has yet to be established. There is a second meaning to the term" activation" as applied to phagocytes that pertains solely to mononuclear phagocytes." Activation" in this second sense refers to a series of changes leading to a generalized increase in destructive power that are elicited in these cells by exposure to endotoxin or the lymphokine, y-interferon. Included among these changes are alterations in the respiratory burst activity ofmaximally stimulated phagocytes. These alterations are most clearly seen with resident peritoneal macrophages, which exhibit almost no respiratory burst when freshly isolated but acquire a substantial capacity to make O2 after 2 or 3 days of culture in the presence ofa suitable activator (31), only to lose this capacity on further culture (32). The mechanism of this second form of activation has received little attention; in all likelihood, it will turn out to involve major changes in gene expression induced by the activating agent.