Kishimoto S, Shimadzu W, Izumi T, Shimizu T, Fukuda T, Makino S, Sugiura T, Waku K
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
J Immunol. 1996 Nov 1;157(9):4126-32.
Platelet-activating factor (PAF) and IL-5 are both important mediators of various allergic reactions, although the relationship between these mediators in allergic responses has not yet been fully elucidated. In this study, we investigated the effects of human rIL-5 on the expression of the PAF receptor (PAF-R) on eosinophils from healthy human volunteers. The specific binding of [3H]WEB 2086, a specific ligand for PAF-R, to eosinophils treated with 5 ng/ml of IL-5 for 12 h was significantly higher than that to untreated cells. The Bmax value for IL-5-treated eosinophils was 1.8-fold higher than that for untreated cells, while the Kd values remained unchanged. This clearly indicates that surface expression of PAF-R on eosinophils is enhanced by IL-5. The enhancement was first observed at 6 h and reached a plateau at 12 to 18 h. The effect of IL-5 was abolished in the presence of cycloheximide or actinomycin D. When the relative amount of PAF-R mRNA was determined by reverse transcription PCR, the message was found to be increased through activation of transcription of transcript 1 on exposure to IL-5. Furthermore, we found that the PAF-induced increase in intracellular calcium ion concentration in eosinophils was markedly augmented by exposure to IL-5 for 12 h. Several lines of data suggest that the enhanced expression of PAF-R on eosinophils due to IL-5 is the cause of the augmented response to PAF. These findings will be of value for understanding the mechanisms of selective infiltration and activation of eosinophils in allergic diseases in which PAF and IL-5 are crucially involved.
血小板活化因子（PAF）和白细胞介素-5（IL-5）都是各种过敏反应的重要介质，尽管这些介质在过敏反应中的关系尚未完全阐明。在本研究中，我们调查了人重组IL-5对健康人类志愿者嗜酸性粒细胞上PAF受体（PAF-R）表达的影响。PAF-R的特异性配体[3H]WEB 2086与用5 ng/ml IL-5处理12小时的嗜酸性粒细胞的特异性结合显著高于未处理细胞。IL-5处理的嗜酸性粒细胞的Bmax值比未处理细胞高1.8倍，而Kd值保持不变。这清楚地表明IL-5增强了嗜酸性粒细胞上PAF-R的表面表达。这种增强在6小时时首次观察到，并在12至18小时达到平台期。在存在环己酰亚胺或放线菌素D的情况下，IL-5的作用被消除。当通过逆转录PCR测定PAF-R mRNA的相对量时，发现该信息通过暴露于IL-5时转录本1的转录激活而增加。此外，我们发现暴露于IL-5 12小时后，PAF诱导的嗜酸性粒细胞内钙离子浓度增加明显增强。多项数据表明，IL-5导致嗜酸性粒细胞上PAF-R表达增强是对PAF反应增强的原因。这些发现对于理解PAF和IL-5至关重要的过敏性疾病中嗜酸性粒细胞的选择性浸润和激活机制具有重要价值。
