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The Journal of Immunology, 2000, 165: 5509-5517.
Copyright © 2000 by The American Association of Immunologists

Eosinophil Major Basic Protein-1 Does Not Contribute to Allergen-Induced Airway Pathologies in Mouse Models of Asthma1

Karen L. Denzler, Steven C. Farmer, Jeffrey R. Crosby, Michael Borchers, Grzegorz Cieslewicz, Kirsten A. Larson2, Stephania Cormier-Regard, Nancy A. Lee3 and James J. Lee3

Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Samuel C. Johnson Medical Research Building, Scottsdale, AZ 85259

The relationship between eosinophils and the development of Ag-induced pulmonary pathologies, including airway hyper-responsiveness, was investigated using mice deficient for the secondary granule component, major basic protein-1 (mMBP-1). The loss of mMBP-1 had no effect on OVA-induced airway histopathologies or inflammatory cell recruitment. Lung function measurements of knockout mice demonstrated a generalized hyporeactivity to methacholine-induced airflow changes (relative to wild type); however, this baseline phenotype was observable only with methacholine; no relative airflow changes were observed in response to another nonspecific stimulus (serotonin). Moreover, OVA sensitization/aerosol challenge of wild-type and mMBP-1-/- mice resulted in identical dose-response changes to either methacholine or serotonin. Thus, the airway hyper-responsiveness in murine models of asthma occurs in the absence of mMBP-1.




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