Induction of functional IL-8 receptors by IL-4 and IL-13 in human monocytes

IL-8 and related Glu-Leu-Arg (ELR+) CXC chemokines are potent chemoattracta nts for neutrophils but not for monocytes, IL-13 and IL-4 strongly increase d CXCR1 and CXCR2 chemokine receptor expression in human monocytes, macroph ages, and dendritic cells. The effect was receptor- and cell type-selective , in that CCRs were not increased and no augmentation was seen in neutrophi ls, The effect was rapid, starting at 4 h, and concentration dependent (EC5 0 = 6.2 and 8.3 ng/ml for CXCR1 and CXCR2, respectively) and caused by new transcriptional activity, IL-13/IL-4-treated monocytes showed increased CXC R1 and CXCR2 membrane expression. IL-8 and related ELR+ chemokines were pot ent and effective chemotactic agents for IL-13/IL-4-treated monocytes, but not for untreated mononuclear phagocytes, with activity comparable to that of reference monocyte attractants, such as MCP-1. In the same cells, IL-8 a lso caused superoxide release. Macrophages and dendritic cells present in b iopsies from Omenn's syndrome and atopic dermatitis patients, two Th2 skewe d pathologies, expressed IL-8 receptors by immunohistochemistry, These resu lts show that IL-13 and IL-4 convert IL-8 and related ELR+ chemokines, prot otypic neutrophil attractants, into monocyte; chemotactic agonists, by up-r egulating receptor expression. Therefore, IL-8 and related chemokines may c ontribute to the accumulation and positioning of mononuclear phagocytes in Th2-dominated responses.