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The Role of Mindin in Allergic Airways Disease

¹ Division of Pulmonary, Allergy, and Critical Care Medicine, and ² Department of Immunology, Duke University Medical Center, Durham, North Carolina; and ³ Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Correspondence and requests for reprints should be addressed to John W. Hollingsworth, M.D., Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Box 103004, Durham, NC 27710. E-mail: holli017{at}mc.duke.edu

Asthma remains a major cause of morbidity and hospitalizations in developed nations. Despite the widespread prevalence of this disease, the genetic and environmental factors that mediate development and progression of allergic airways disease remain poorly understood. Pulmonary recruitment of eosinophils is believed to contribute to many cardinal features of allergic airways disease. Therefore, it is paramount to understand host factors which contribute to pulmonary eosinophil recruitment into the lungs. Mindin is a component of pulmonary extracellular matrix which can regulate inflammatory cell recruitment. We characterized the role of mindin in the severity of allergic airways disease using established murine models. There were no baseline differences in wild-type and mindin-deficient animals in either cell counts or airway physiology. Using the ovalbumin murine model of allergic airways disease, we observed that mindin-deficient animals have less severe allergic airways disease, with fewer lung eosinophils and lower lung lavage levels of inflammatory Th2 cytokines such as IL-13 and IL-4. Furthermore, mindin-deficient animals have reduced airway hyperresponsiveness after methacholine challenge. To determine the role of mindin in eosinophil trafficking independent of antigen immunization or T-lymphocyte activation, we directly instilled IL-13 into the lungs of mice. In this model, mindin regulates eosinophil recruitment into the lung. In vitro experiments demonstrate that mindin can enhance eotaxin-mediated eosinophil adhesion and migration. In conclusion, these data suggest that the pulmonary matrix protein, mindin, contributes to the development and severity of allergic airways disease.

FOOTNOTES

Supported by the National Institute of Environmental Health Services (ES11961) and the National Heart, Lung, and Blood Institute (HL91335).

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form June 11, 2008; accepted in final form November 4, 2008)

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Li, Z. Articles by Hollingsworth, J. W. Search for Related Content PubMed Articles by Li, Z. Articles by Hollingsworth, J. W.