IL-5 up-regulates cysteinyl leukotriene 1 receptor expression in HL-60 cells differentiated into eosinophils

The cysteinyl leukotrienes, leukotriene (LT) C-4, LTD4, and LTE4, are lipid mediators that have been implicated in the pathogenesis of Several inflamm atory processes, including asthma. The human LTD4 receptor, CysLT(1)R, was recently cloned and characterized. We had previously shown that HL-60 cells differentiated toward the eosinophilic lineage (HL-60/eos) developed speci fic functional LTD4 receptors, The present work was undertaken to study the potential modulation of CysLT(1)R expression in HL-60/eos by IL-5, an impo rtant regulator of eosinophil function, Here, we report that IL-5 rapidly u p-regulates CysLT(1)R mRNA expression, with consequently enhanced CysLT(1)R protein expression and function in HL-60/eos, CysLT(1)R mRNA expression wa s augmented 2- to 15-fold following treatment with IL-5 (1-20 ng/ml), The e ffect was seen after 2 h, was maximal by 4 h, and maintained at 8 h, Althou gh CysLT(1)R mRNA was constitutively expressed in undifferentiated HL-60 ce lls, its expression was not modulated by IL-5 in the absence of differentia tion. Differentiated HL-60/eos cells pretreated with IL-5 (10 ng/ml) for 24 h showed enhanced CysLT(1)R expression on the cell surface, as assessed by how cytometry using a polyclonal anti-CysLT(1)R Ab, They also showed enhan ced responsiveness to LTD4, but not to LTB4 or platelet-activating factor, in terms of Ca2+ mobilization, and augmented the chemotactic response to LT D4. Our findings suggest a possible mechanism by which IL-5 can modulate eo sinophil functions and particularly their responsiveness to LTD4, and thus contribute to the pathogenesis of asthma and allergic diseases.