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首页> 外文期刊>Journal of cellular biochemistry. >Amphotericin B both inhibits and enhances T-cell proliferation: inhibitory effect is mediated through H(2)O(2) production via cyclooxygenase pathway by macrophages.
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Amphotericin B both inhibits and enhances T-cell proliferation: inhibitory effect is mediated through H(2)O(2) production via cyclooxygenase pathway by macrophages.

机译：两性霉素B既抑制又增强T细胞增殖：抑制作用是通过巨噬细胞通过环氧合酶途径的H（2）O（2）产生的。

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摘要

Amphotericin B (AmB) has been shown to have both immunosuppressive and -enhancing effects, making its precise nature of action enigmatic. In the present study, we found that AmB inhibited concanavalin A (Con A)-induced T cell proliferation if added within first 30 min of stimulation, after which inhibition began to diminish rapidly. However, AmB did not inhibit T-cell proliferation induced by a combination of PMA and ionomycin. AmB inhibition of Con A-induced proliferation was completely overcome by cyclooxygenase inhibitor ibuprofen ([alpha-methyl-4-(isobutyl)phenylacetic acid]) and H(2)O(2) scavenger catalase. In fact, in the presence of ibuprofen and catalase, AmB enhanced, instead of suppressing, Con A-induced proliferation in a dose-dependent way. The effect of catalase was limited to the removal of extracellular H(2)O(2) only, as the enzyme did not enter the cells. AmB stimulated H(2)O(2) production by macrophages, but not by a lymphocyte population, which was inhibited by ibuprofen. Our T-cell preparation contained about 3% macrophages, and AmB inhibition of proliferation was further pronounced by increasing the macrophage number by as little as 1%. Finally, AmB inhibition of Con A-induced T-cell proliferation was completely overcome by 2-mercaptoethanol. On the basis of these results, we suggest that AmB stimulates H(2)O(2) production by macrophages through the activation of the cyclooxygenase pathway of arachidonate metabolism. H(2)O(2) then inhibits Con A-induced T-cell proliferation by interfering with an early step of the T-cell receptor signaling pathway through the oxidative modification of some signaling proteins. Our results also show that AmB enhances T-cell proliferation, which can be seen only after blocking its inhibitory effect. Copyright 2000 Wiley-Liss, Inc.
机译：两性霉素B（AmB）已被证明具有免疫抑制和增强作用，使其确切的作用性质难以捉摸。在本研究中，我们发现，如果在刺激的前30分钟内添加AmB，会抑制伴刀豆球蛋白A（Con A）诱导的T细胞增殖，此后抑制作用开始迅速减弱。但是，AmB不能抑制PMA和离子霉素的组合诱导的T细胞增殖。环氧化酶抑制剂布洛芬（[α-甲基-4-（异丁基）苯基乙酸]）和H（2）O（2）清除剂过氧化氢酶完全克服了对Con A诱导的AmB的抑制作用。实际上，在布洛芬和过氧化氢酶的存在下，AmB以剂量依赖性方式增强而不是抑制Con A诱导的增殖。过氧化氢酶的作用仅限于去除细胞外H（2）O（2），因为该酶没有进入细胞。 AmB刺激巨噬细胞产生H（2）O（2），但没有被布洛芬抑制的淋巴细胞种群。我们的T细胞制备物含有约3％的巨噬细胞，通过将巨噬细胞数目增加低至1％，AmB对增殖的抑制作用更加明显。最后，2-巯基乙醇完全克服了AmB对Con A诱导的T细胞增殖的抑制作用。根据这些结果，我们建议AmB刺激巨噬细胞通过激活花生四烯酸代谢的环氧合酶途径H（2）O（2）生产。然后，H（2）O（2）通过干扰某些信号蛋白的氧化修饰来干扰T细胞受体信号传导途径的早期步骤，从而抑制Con A诱导的T细胞增殖。我们的结果还表明，AmB增强T细胞增殖，只有在阻断其抑制作用后才能看到。版权所有2000 Wiley-Liss，Inc.

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