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Am J Physiol Lung Cell Mol Physiol (September 13, 2002). doi:10.1152/ajplung.00260.2002
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Articles in PresS, published online ahead of print September 13, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00260.2002
Submitted on August 2, 2002
Accepted on September 12, 2002

Albation of eosinophils leads to a reduction of allergen-induced pulmonary pathology

J. Paul Justice1, Michael T. Borchers2, Jeffrey R. Crosby1, Edith M. Hines1, Huahao H. Shen3, Sergei I. Ochkur2, Michael P. McGarry2, Nancy A. Lee1, and James J. Lee2*

1 Division of Hematology/Oncology, Mayo Clinic Scottsdale, Scottsdale, AZ, USA
2 Division of Pulmonary Medicine, Mayo Clinic Scottsdale, Scottsdale, AZ, USA
3 Department of Respiratory Medicine, Second Hospital, Zhejiang University College of Medicine, HangZhou, PR, China

* To whom correspondence should be addressed. E-mail: jjlee{at}mayo.edu.

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.




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