title: CC chemokine receptors 1 and 3 are differentially regulated by IL-5 during maturation of eosinophilic HL-60 cells.
abstract: CC chemokine receptors 1 and 3 (CCR1 and CCR3) are expressed by eosinophils; however, factors regulating their expression and function have not previously been defined. Here we analyze chemokine receptor expression and function during eosinophil differentiation, using the eosinophilic 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 not specifically bind CC chemokines. Cells treated with butyric acid acquired eosinophil characteristics; expressed mRNA for CCR1 and CCR3, but not for CCR4 or CCR5; acquired specific binding sites for macrophage-inflammatory protein-1alpha and eotaxin (the selective ligands for CCR1 and CCR3, respectively); and exhibited specific calcium flux and chemotaxis responses to macrophage-inflammatory protein-1alpha, eotaxin, and other known CCR1 and CCR3 agonists. CCR3 was expressed later and at lower levels than CCR1 and could be further induced by IL-5, whereas IL-5 had little or no effect on CCR1 expression. Consistent with the HIV-1 coreceptor activity of CCR3, HL-60 clone 15 cells induced with butyric acid and IL-5 fused with HeLa cells expressing CCR3-tropic HIV-1 envelope glycoproteins, and fusion was blocked specifically by eotaxin or an anti-CCR3 mAb. These data suggest that CCR1 and CCR3 are markers of late eosinophil differentiation that are differentially regulated by IL-5 in this model.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Tiffany
authors.forename: G
authors.initials: G
authors.lastname: Alkhatib
authors.forename: C
authors.initials: C
authors.lastname: Combadiere
authors.forename: E A
authors.initials: EA
authors.lastname: Berger
authors.forename: P M
authors.initials: PM
authors.lastname: Murphy
mesh_terms: D001665:Binding Sites / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002459:Cell Fusion / Q000276:immunology; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002999:Clone Cells; D004804:Eosinophils / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D015686:Gene Products, env / Q000502:physiology; D015497:HIV-1 / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D015848:Interleukin-5 / Q000502:physiology*; D008024:Ligands; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C515300:CCR1 protein, human; C515350:CCR3 protein, human; D002631:Chemotactic Factors, Eosinophil; D015686:Gene Products, env; D015848:Interleukin-5; D008024:Ligands; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D002118:Calcium