Dual signaling and effector pathways mediate human eosinophil activation by platelet-activating factor
Dual signaling and effector pathways mediate human eosinophil activation by platelet-activating factor
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DOI：
10.1159/000077791
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发表时间：
2004-01-01
影响因子：
2.8
通讯作者：
Kimura, H
中科院分区：
文献类型：
--
作者：
Kato, M;Kita, H;Kimura, H
血小板活化因子（PAF）诱导嗜酸性粒细胞的多种细胞功能，包括趋化性、粘附、超氧阴离子（O-2（-））产生和脱粒。虽然PAF与其他趋化因子如N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸、补体片段和脂质介质具有许多生物学效应，但PAF的独特之处在于其作用对百日咳毒素（PTX）具有相对抗性，并且比中性粒细胞更强烈地激活嗜酸性粒细胞。在这篇综述中，我们考虑如何PAF可能会激活人类嗜酸性粒细胞优先于中性粒细胞，并讨论可能的机制，PAF诱导的激活人类嗜酸性粒细胞通过两个不同的信号和效应途径。最近，我们分析了O-2（-）生产嗜酸性粒细胞使用灵敏，实时化学发光法。我们的研究结果表明，在人类嗜酸性粒细胞PAF激活两个不同的信号和效应途径耦合到PAF受体：一个连接到PTX敏感的G蛋白（S），另一个连接到PTX耐药的G蛋白（S），磷脂酰肌醇3-激酶，和细胞粘附。嗜酸性粒细胞PAF受体对两种不同G蛋白的激活可能解释了人嗜酸性粒细胞对PAF的强烈和多样的生物学反应。版权所有（C）2004 S. Karger AG，巴塞尔。
Platelet-activating factor (PAF) induces various cellular functions in eosinophils including chemotaxis, adhesion, superoxide anion (O-2(-)) production, and degranulation. While PAF shares many biological effects with other chemotactic factors such as N-formyl-methionyl-leucyl-phenylalanine, complement fragments, and lipid mediators, PAF is unique in that its action is relatively resistant to pertussis toxin (PTX), and in activating eosinophils more strongly than neutrophils. In this review we consider how PAF might activate human eosinophils in preference to neutrophils, and discuss possible mechanisms of PAF-induced activation of human eosinophils via two distinct signaling and effector pathways. Recently we analyzed O-2(-) production by eosinophils using a sensitive, real-time chemiluminescence method. Our results showed that in human eosinophils PAF activates two distinct signaling and effector pathways coupled to the PAF receptor: one linked to PTX-sensitive G protein(s) and another to PTX-resistant G protein( s), phosphatidylinositol 3-kinase, and cellular adhesion. This activation of two different G proteins by the eosinophil PAF receptor may explain the strong and diverse biological responses of human eosinophils to PAF. Copyright (C) 2004 S. Karger AG, Basel.