INHIBITION OF THE PHAGOCYTOSIS-INDUCED RESPIRATORY BURST BY THE FUNGAL METABOLITE WORTMANNIN AND SOME ANALOGS
INHIBITION OF THE PHAGOCYTOSIS-INDUCED RESPIRATORY BURST BY THE FUNGAL METABOLITE WORTMANNIN AND SOME ANALOGS
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DOI：
10.1016/0014-4827(87)90201-1
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发表时间：
1987-04-01
影响因子：
3.7
通讯作者：
PAYNE, TG
中科院分区：
文献类型：
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作者：
BAGGIOLINI, M;DEWALD, B;PAYNE, TG
甾醇类真菌代谢产物渥曼青霉素和一些天然的和化学衍生的类似物被发现可以阻断吞噬过程中呼吸爆发的诱导。17-羟基渥曼青霉素，最活跃的化合物测试，显示了50%的抑制爆发在中性粒细胞和单核细胞吞噬细胞在0.8和17 nM之间的浓度范围，而渥曼青霉素本身是约一半的效力。化学衍生表明，环A和环B之间具有相邻羰基官能团的呋喃结构对于活性是必需的。在完全阻止超氧化物或过氧化氢产生的浓度下，渥曼菌素没有细胞毒性，也不抑制吞噬作用。在甚至更高的浓度（10 μ M）下，一旦激活，17-羟基渥曼青霉素对NADPH氧化酶没有影响。这表明渥曼菌素干扰了颗粒刺激引发的信号转导序列，并导致呼吸爆发氧化酶的激活。
The sterol-like fungal metabolite wortmannin and a number of natural and chemically-derived analogues were found to block the induction of the respiratory burst during phagocytosis. 17-Hydroxy wortmannin, the most active compound tested, showed a 50% inhibition of the burst in neutrophils and mononclear phagocytes at concentrations ranging between 0.8 and 17 nM, while wortmannin itself was about half as potent. Chemical derivation showed that a furane structure between ring A and B with adjacent carbonyl functions is essential for activity. At concentrations that entirely prevented superoxide or hydrogen peroxide production, the wortmannins were not cytotoxic and did not inhibit phagocytosis. At even higher concentrations (10 .mu.M), 17-hydroxy wortmannin had no effect on the NADPH oxidase, once activated. This suggests that the wortmannins interfere with the signal transduction sequence initiated by the particulate stimulus and leading to the activation of the respiratory burst oxidase.