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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 297/5/L931    most recent 00150.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Sajjan, U. Articles by Hershenson, M. B. PubMed PubMed Citation Articles by Sajjan, U. Articles by Hershenson, M. B.

Elastase- and LPS-exposed mice display altered responses to rhinovirus infection

Departments ¹of Pediatrics and Communicable Diseases, ; ²Molecular and Integrative Physiology, and ; ³Internal Medicine, University of Michigan, Ann Arbor; and ; ⁴Medical Service, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan

Submitted 6 May 2009 ; accepted in final form 10 September 2009

Viral infection is associated with approximately one-half of acute exacerbations of chronic obstructive pulmonary disease (COPD), which in turn, accelerate disease progression. In this study, we infected mice exposed to a combination of elastase and LPS, a constituent of cigarette smoke and a risk factor for development of COPD, with rhinovirus serotype 1B, and examined animals for viral persistence, airway resistance, lung volume, and cytokine responses. Mice exposed to elastase and LPS once a week for 4 wk showed features of COPD such as airway inflammation and obstruction, goblet cell metaplasia, reduced lung elastance, increased total lung volume, and increased alveolar chord length. In general, mice exposed to elastase or LPS alone showed intermediate effects. Compared with rhinovirus (RV)-infected PBS-exposed mice, RV-infected elastase/LPS-exposed mice showed persistence of viral RNA, airway hyperresponsiveness, increased lung volume, and sustained increases in expression of TNF, IL-5, IL-13, and muc5AC (up to 14 days postinfection). Furthermore, virus-induced IFNs, interferon response factor-7, and IL-10 were deficient in elastase/LPS-treated mice. Mice exposed to LPS or elastase alone cleared virus similar to PBS-treated control mice. We conclude that limited exposure of mice to elastase/LPS produces a COPD-like condition including increased persistence of RV, likely due to skewing of the immune response towards a Th2 phenotype. Similar mechanisms may be operative in COPD.

chronic obstructive pulmonary disease; goblet cell metaplasia; IL-10; innate immunity; interferons