The extracellular matrix protein mindin regulates trafficking of murine eosinophils into the airspace.

Journal Article (Journal Article)

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 that 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 cell counts or airway physiology. Using the OVA murine model of allergic airways disease, we observed that mindin-deficient animals have less-severe allergic airways disease with fewer airspace eosinophils and lower lung-lavage levels of inflammatory Th2 cytokines such as IL-13 and IL-4. Furthermore, mindin-deficient animals have reduced airway hyper-responsiveness after methacholine challenge. To determine the role of mindin in eosinophil trafficking, independent of antigen immunization or T lymphocyte activation, we instilled IL-13 directly into the lungs of mice. In this model, mindin regulates eosinophil recruitment into the airspace. In vitro experiments demonstrate that mindin can enhance eotaxin-mediated eosinophil adhesion and migration, which are dependent on the expression of integrins alphaMbeta2 and alpha4beta1. In conclusion, these data suggest that mindin participates in integrin-dependent trafficking of eosinophils and can contribute to the severity of allergic airways disease.

Full Text

Duke Authors

Cited Authors

  • Li, Z; Garantziotis, S; Jia, W; Potts, EN; Lalani, S; Liu, Z; He, Y-W; Foster, WM; Hollingsworth, JW

Published Date

  • January 2009

Published In

Volume / Issue

  • 85 / 1

Start / End Page

  • 124 - 131

PubMed ID

  • 18818374

Pubmed Central ID

  • PMC2626769

International Standard Serial Number (ISSN)

  • 0741-5400

Digital Object Identifier (DOI)

  • 10.1189/jlb.0208135


  • eng

Conference Location

  • United States