title: Ablation of eosinophils leads to a reduction of allergen-induced pulmonary pathology.
abstract: A strategy to deplete eosinophils from the lungs of ovalbumin (OVA)-sensitized/challenged mice was developed using antibody-mediated depletion. Concurrent administration [viz. the peritoneal cavity (systemic) and as an aerosol to the lung (local)] of a rat anti-mouse CCR3 monoclonal antibody resulted in the abolition of eosinophils from the lung such that the airway lumen was essentially devoid of eosinophils. Moreover, perivascular/peribronchial eosinophil numbers were reduced to levels indistinguishable from saline-challenged animals. This antibody-mediated depletion was not accompanied by effects on any other leukocyte population, including, but not limited to, T cells and mast cells/basophils. In addition, no effects were observed on other underlying allergic inflammatory responses in OVA-treated mice, including OVA-specific immunoglobulin production as well as T cell-dependent elaboration of Th2 cytokines. The ablation of virtually all pulmonary eosinophils in OVA-treated mice (i.e., without concurrent effects on T cell activities) resulted in a significant decrease in mucus accumulation and abolished allergen-induced airway hyperresponsiveness. These data demonstrate a direct causative relationship between allergen-mediated pulmonary pathologies and eosinophils.
authors.affiliation: Division of Hematology/Oncology and Pulmonary Medicine, Department of Biochemistry and Molecular Biology, S. C. Johnson Medical Research Building, Mayo Clinic Scottsdale, 13400 E. Shea Boulevard, Scottsdale, AZ 85259, USA.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Justice
authors.forename: Michael T
authors.initials: MT
authors.lastname: Borchers
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Crosby
authors.forename: Edith M
authors.initials: EM
authors.lastname: Hines
authors.forename: Huahao H
authors.initials: HH
authors.lastname: Shen
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Ochkur
authors.forename: Michael P
authors.initials: MP
authors.lastname: McGarry
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000917:Antibody Formation; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D020397:Goblet Cells / Q000473:pathology; D007136:Immunoglobulins / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology*; D051381:Rats; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000276:immunology; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; C515351:Ccr3 protein, mouse; C515352:Ccr3 protein, rat; D016207:Cytokines; D007136:Immunoglobulins; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D010047:Ovalbumin