Eotaxin potentiates antigen-dependent basophil IL-4 production.
Basophils are a major source of IL-4, which is a critical factor in the generation of allergic inflammation. Eotaxin induces chemotaxis mediated through the CC chemokine receptor 3 (CCR3) present on basophils as well as eosinophils and Th2 cells, thereby promoting cell recruitment. To determine whether eotaxin has other proinflammatory activity, we examined the effect of eotaxin on basophil IL-4 expression by flow cytometry. Eotaxin alone had no effect on basophil IL-4 production, but further increased allergen-stimulated IL-4 expression. Eotaxin also enhanced IL-4 release from purified basophils 2- to 4-fold, as determined by ELISA (p < 0.01). Addition of eotaxin to cultures resulted in a 40-fold left shift in the dose response to Ag. This effect was obtained with physiologic concentrations of eotaxin (10 ng/ml), was abrogated by an Ab to the CCR3 receptor, and was noted with other chemokine ligands of CCR3. Additionally, eotaxin augmented IL-3 priming of basophil IL-4 production in a synergistic manner (p < 0.01). In contrast, no priming was observed with either IL-5 or GM-CSF. These results establish a novel function for eotaxin and other chemokine ligands of CCR3: the potentiation of Ag-mediated IL-4 production in basophils, and suggest a potential nonchemotactic role for CC chemokines in the pathogenesis and amplification of inflammation.
Devouassoux
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Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Metcalfe
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Prussin
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000941:Antigens / Q000502:physiology*; D001249:Asthma / Q000276:immunology; D001491:Basophils / Q000276:immunology* / Q000378:metabolism*; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis*; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000502:physiology
D000276:Adjuvants, Immunologic; D000941:Antigens; C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D007377:Interleukin-3; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D015847:Interleukin-4