title: CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation.
abstract: The CC chemokine receptor 3 (CCR3) is expressed by eosinophils, mast cells, and Th2 cells. We used CCR3(-/-) mice to assess the role of CCR3 in a murine model of allergic skin inflammation induced by repeated epicutaneous sensitization with ovalbumin (OVA), and characterized by eosinophil skin infiltration, local expression of Th2 cytokines, and airway hyperresponsiveness (AHR) to inhaled antigen. Eosinophils and the eosinophil product major basic protein were absent from the skin of sham and OVA-sensitized CCR3(-/-) mice. Mast cell numbers and expression of IL-4 mRNA were normal in skin of CCR3(-/-) mice, suggesting that CCR3 is not important for infiltration of the skin by mast cells and Th2 cells. CCR3(-/-) mice produced normal levels of OVA-specific IgE, and their splenocytes secreted normal amounts of IL-4 and IL-5 following in vitro stimulation with OVA, indicating effective generation of systemic Th2 helper responses. Recruitment of eosinophils to lung parenchyma and bronchoalveolar lavage (BAL) fluid was severely impaired in CCR3(-/-) mice, which failed to develop AHR to methacholine following antigen inhalation. These results suggest that CCR3 plays an essential role in eosinophil recruitment to the skin and the lung and in the development of AHR.
authors.affiliation: Division of Immunology and Department of Pediatrics, Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Weilie
authors.initials: W
authors.lastname: Ma
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bryce
authors.forename: Alison A
authors.initials: AA
authors.lastname: Humbles
authors.forename: Dhafer
authors.initials: D
authors.lastname: Laouini
authors.forename: Ali
authors.initials: A
authors.lastname: Yalcindag
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Friend
authors.forename: Hans C
authors.initials: HC
authors.lastname: Oettgen
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Raif S
authors.initials: RS
authors.lastname: Geha
mesh_terms: D000818:Animals; D003876:Dermatitis, Atopic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology
chemical_list: C515350:CCR3 protein, human; C515351:Ccr3 protein, mouse; D015848:Interleukin-5; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin