title: Eosinophils contribute to the resolution of lung-allergic responses following repeated allergen challenge.
abstract: BACKGROUND
  Eosinophils accumulate at the site of allergic inflammation and are critical effector cells in allergic diseases. Recent studies have also suggested a role for eosinophils in the resolution of inflammation.
  
  
  OBJECTIVE
  To determine the role of eosinophils in the resolution phase of the response to repeated allergen challenge.
  
  
  METHODS
  Eosinophil-deficient (PHIL) and wild-type (WT) littermates were sensitized and challenged to ovalbumin (OVA) 7 or 11 times. Airway inflammation, airway hyperresponsiveness (AHR) to inhaled methacholine, bronchoalveolar lavage (BAL) cytokine levels, and lung histology were monitored. Intracellular cytokine levels in BAL leukocytes were analyzed by flow cytometry. Groups of OVA-sensitized PHIL mice received bone marrow from WT or IL-10(-/-) donors 30 days before the OVA challenge.
  
  
  RESULTS
  PHIL and WT mice developed similar levels of AHR and numbers of leukocytes and cytokine levels in BAL fluid after OVA sensitization and 7 airway challenges; no eosinophils were detected in the PHIL mice. Unlike WT mice, sensitized PHIL mice maintained AHR, lung inflammation, and increased levels of IL-4, IL-5, and IL-13 in BAL fluid after 11 challenges whereas IL-10 and TGF-β levels were decreased. Restoration of eosinophil numbers after injection of bone marrow from WT but not IL-10-deficient mice restored levels of IL-10 and TGF-β in BAL fluid as well as suppressed AHR and inflammation. Intracellular staining of BAL leukocytes revealed the capacity of eosinophils to produce IL-10.
  
  
  CONCLUSIONS
  After repeated allergen challenge, eosinophils appeared not essential for the development of AHR and lung inflammation but contributed to the resolution of AHR and inflammation by producing IL-10.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colo.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colo.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shiraishi
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colo.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ashino
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colo.
authors.forename: Junyan
authors.initials: J
authors.lastname: Han
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colo.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colo.
authors.forename: Meiqin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Pulmonary Medicine, Mayo Clinic Arizona, Scottsdale, Ariz.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.affiliation: Pulmonary Medicine, Mayo Clinic Arizona, Scottsdale, Ariz.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colo. Electronic address: gelfande@njhealth.org.
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D016026:Bone Marrow Transplantation; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D010047:Ovalbumin
keywords: Eosinophils; IL-10; resolution of inflammation