title: Retinoic acids up-regulate functional eosinophil-driving receptor CCR3.
abstract: Eotaxins and their receptor CCR3 have a definitive role for tissue accumulation of eosinophils both under homeostatic and pathologic conditions. However, physiological stimuli that can up-regulate CCR3 in blood-derived human eosinophils have not been recognized. As a prior gene microarray study revealed up-regulation of CCR3 in eosinophils stimulated with retinoic acids (RAs), the expression of functional CCR3 was examined. We found that 9-cis RA and all-trans RA (ATRA) significantly induced surface CCR3 expression regardless of the presence of IL-3 or IL-5. Pharmacological manipulations with receptor-specific agonists and antagonists indicated that retinoic acid receptor-α activation is critical for CCR3 up-regulation. RA-induced CCR3 was associated with its functional capacity, in terms of the calcium mobilization and chemotactic response to eotaxin-1 (CCL11). Our study suggests an important role of vitamin A derivatives in the tissue accumulation of eosinophils.
authors.affiliation: Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan. ueki-shige@nifty.com
authors.forename: S
authors.initials: S
authors.lastname: Ueki
authors.forename: J
authors.initials: J
authors.lastname: Nishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Y
authors.initials: Y
authors.lastname: Konno
authors.forename: M
authors.initials: M
authors.lastname: Tamaki
authors.forename: M
authors.initials: M
authors.lastname: Itoga
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.forename: Y
authors.initials: Y
authors.lastname: Moritoki
authors.forename: W
authors.initials: W
authors.lastname: Ito
authors.forename: J
authors.initials: J
authors.lastname: Chihara
mesh_terms: D002478:Cells, Cultured; D054423:Chemokine CCL24 / Q000235:genetics / Q000378:metabolism; D002631:Chemotactic Factors, Eosinophil / Q000235:genetics / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000235:genetics; D003876:Dermatitis, Atopic / Q000097:blood* / Q000235:genetics; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D054397:Receptors, CCR3 / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: C515350:CCR3 protein, human; D054423:Chemokine CCL24; D002631:Chemotactic Factors, Eosinophil; D054397:Receptors, CCR3; D014212:Tretinoin
keywords: CCR3; eosinophils; retinoic acids; vitamin A