Tumor necrosis factor as an activator of human granulocytes. Potentiation of the metabolisms triggered by the Ca2+-mobilizing agonists.
Tumor necrosis factor as an activator of human granulocytes. Potentiation of the metabolisms triggered by the Ca2+-mobilizing agonists.
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肿瘤坏死因子作为人粒细胞的激活剂。
DOI：
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发表时间：
1989
影响因子：
4.4
通讯作者：
Fumimaro Takaku
中科院分区：
文献类型：
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作者：
A. Yuo;Seiichi Kitagawa;I. Suzuki;A. Urabe;T. Okabe;Masanobu Saito;Fumimaro Takaku
TNF刺激超氧化物（O2-）以剂量依赖性的方式直接在人粒细胞中释放（1至1000 U/ml），尽管其效力较弱。tnf诱导的O2-释放被cAMP激动剂或离子霉素抑制，并且不伴有胞质游离Ca2+ [（Ca2+]i）和膜电位变化（去极化）的增加。这些发现表明，tnf受体介导的细胞活化既不需要Ca2+动员也不需要膜去极化。用TNF预处理人粒细胞可通过受体介导的Ca2+动员激动剂（FMLP、Con A和小麦胚芽凝集素）或Ca2+离子载体离子霉素平行刺激O2-释放和膜去极化，而不受蛋白激酶C的直接激活剂PMA的刺激。用100 U/ml TNF预处理细胞在37℃下5 ~ 10 min获得最佳效果。虽然增强的幅度根据激动剂用作后续刺激而变化。除Con a外，TNF不影响Ca2+动员激动剂刺激的[Ca2+]i的增加。Con a诱导的[Ca2+]i的增加以剂量依赖性的方式被TNF增强。TNF的这些不同作用可以部分解释为TNF对[Ca2+]i增加引发的代谢事件的独家增强。
TNF stimulated superoxide (O2-) release directly in human granulocytes in a dose-dependent manner (1 to 1000 U/ml), although its potency was weak. TNF-induced O2- release was inhibited by cAMP agonists or ionomycin, and was not accompanied with an increase in cytoplasmic free Ca2+ [( Ca2+]i) and membrane potential changes (depolarization). These findings indicate that neither Ca2+ mobilization nor membrane depolarization is required for TNF-receptor-mediated cell activation. The pretreatment of human granulocytes with TNF enhanced O2- release and membrane depolarization in parallel stimulated by the receptor-mediated Ca2+-mobilizing agonists (FMLP, Con A, and wheat germ agglutinin) or the Ca2+ ionophore ionomycin, but not by PMA, a direct activator of protein kinase C. The optimal effect was obtained by pretreatment of cells with 100 U/ml TNF for 5 to 10 min at 37 degrees C, although the magnitude of enhancement varied according to the agonists used as subsequent stimuli. TNF did not affect an increase in [Ca2+]i stimulated by the Ca2+-mobilizing agonists, except Con A. Con A-induced increase in [Ca2+]i was enhanced by TNF in a dose-dependent manner. These diverse effects of TNF could be partly explained by the exclusive potentiation by TNF of the metabolic events triggered by an increase in [Ca2+]i.