CC-CHEMOKINE RECEPTOR-1 AND RECEPTOR-3 ARE DIFFERENTIALLY REGULATED BY IL-5 DURING MATURATION OF EOSINOPHILIC HL-60 CELLS

CC chemokine receptors I and 3 (CCR1 and CCR3) are expressed by eosino phils; however, factors regulating their expression and function have not previously been defined, Here we analyze chemokine receptor expres sion and function during eosinophil differentiation, using the eosinop hilic cell line HL-60 clone 15 as a model system, RNA for CCR1, -3, -4 , and -5 was not detectable in the parental cells, and the cells did n ot specifically bind CC chemokines, Cells treated with butyric acid ac quired eosinophil characteristics; expressed mRNA for CCR1 and CCR3, b ut not for CCR4 or CCR5; acquired specific binding sites for macrophag e-inflammatory protein-1 alpha and eotaxin (the selective ligands for CCR1 and CCR3, respectively); and exhibited specific calcium flux and chemotaxis responses to macrophage-inflammatory protein-1 alpha; eotax in, and other known CCR1 and CCR3 agonists, CCR3 was expressed later a nd at lower levels than CCR1 and could be further induced by IL-5, whe reas IL-5 had little or no effect on CCR1 expression, Consistent with the HIV-I coreceptor activity of CCR3, HL-60 clone 15 cells induced wi th butyric acid and IL-5 fused with HeLa cells expressing CCR3-tropic HIV-1 envelope glycoproteins, and fusion was blocked specifically by e otaxin or an anti-CCR3 mAb. These data suggest that CCR1 and CCR3 are markers of late eosinophil differentiation that are differentially reg ulated by IL-5 in this model.