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* Department of Pathology, University of Vermont, Burlington VT 05405;
Department of Respiratory Medicine, Maastricht University, Maastricht, The Netherlands; and
Department of Medicine, University of Vermont, Burlington VT 05405
Oxidative stress is a hallmark of asthma, and increased levels of oxidants are considered markers of the inflammatory process. Most studies to date addressing the role of oxidants in the etiology of asthma were based on the therapeutic administration of low m.w. antioxidants or antioxidant mimetic compounds. To directly address the function of endogenous hydrogen peroxide in the pathophysiology of allergic airway disease, we comparatively evaluated mice systemically overexpressing catalase, a major antioxidant enzyme that detoxifies hydrogen peroxide, and C57BL/6 strain matched controls in the OVA model of allergic airways disease. Catalase transgenic mice had 8-fold increases in catalase activity in lung tissue, and had lowered DCF oxidation in tracheal epithelial cells, compared with C57BL/6 controls. Despite these differences, both strains showed similar increases in OVA-specific IgE, IgG1, and IgG2a levels, comparable airway and tissue inflammation, and identical increases in procollagen 1 mRNA expression, following sensitization and challenge with OVA. Unexpectedly, mRNA expression of MUC5AC and CLCA3 genes were enhanced in catalase transgenic mice, compared with C57BL/6 mice subjected to Ag. Furthermore, when compared with control mice, catalase overexpression increased airway hyperresponsiveness to methacholine both in naive mice as well as in response to Ag. In contrast to the prevailing notion that hydrogen peroxide is positively associated with the etiology of allergic airways disease, the current findings suggest that endogenous hydrogen peroxide serves a role in suppressing both mucus production and airway hyperresponsiveness.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health (RO1 HL60014 and HL60812), Public Health Service (P20 RL15557), National Center for Research Resources, Centers of Biomedical Research Excellence (PO1 HL67004), and a grant from the Dutch Asthma Foundation.
2 Address correspondence and reprint requests to Dr. Yvonne M. W. Janssen-Heininger, Department of Pathology, University of Vermont, HSRF Building, Room 216A, Burlington, VT 05405. E-mail address: yjanssen{at}uvm.edu
3 Abbreviations used in this paper: BAL, bronchoalveolar lavage; RT, room temperature.
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