Regulation by IL-5 of expression of functional platelet-activating factor receptors on human eosinophils

Abstract

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.