Endogenous osteopontin promotes ozone-induced neutrophil recruitment to the lungs and airway hyperresponsiveness to methacholine

Ramon X. Barreno, Jeremy B. Richards, Daniel J. Schneider, Kevin R. Cromar, Arthur J. Nadas, Christopher B. Hernandez, Lance M. Hallberg, Roger E. Price, Syed S. Hashmi, Michael R. Blackburn, Ikram U. Haque, Richard A. Johnston

    Research output: Contribution to journalArticle

    17 Scopus citations

    Abstract

    Inhalation of ozone (O3), a common environmental pollutant, causes pulmonary injury, pulmonary inflammation, and airway hyperresponsiveness (AHR) in healthy individuals and exacerbates many of these same sequelae in individuals with preexisting lung disease. However, the mechanisms underlying these phenomena are poorly understood. Consequently, we sought to determine the contribution of osteopontin (OPN), a hormone and a pleiotropic cytokine, to the development of O3-induced pulmonary injury, pulmonary inflammation, and AHR. To that end, we examined indices of these aforementioned sequelae in mice genetically deficient in OPN and in wild-type, C57BL/6 mice 24 h following the cessation of an acute (3 h) exposure to filtered room air (air) or O3 (2 parts/million). In wild-type mice, O3 exposure increased bronchoalveolar lavage fluid (BALF) OPN, whereas immunohistochemical analysis demonstrated that there were no differences in the number of OPN-positive alveolar macrophages between air- and O3-exposed wild-type mice. O3 exposure also increased BALF epithelial cells, protein, and neutrophils in wild-type and OPN-deficient mice compared with genotype-matched, air-exposed controls. However, following O3 exposure, BALF neutrophils were significantly reduced in OPN-deficient compared with wild-type mice. When airway responsiveness to inhaled acetyl-β-methylcholine chloride (methacholine) was assessed using the forced oscillation technique, O3 exposure caused hyperresponsiveness to methacholine in the airways and lung parenchyma of wild-type mice, but not OPN-deficient mice. These results demonstrate that OPN is increased in the air spaces following acute exposure to O3 and functionally contributes to the development of O3-induced pulmonary inflammation and airway and lung parenchymal hyperresponsiveness to methacholine.

    Original languageEnglish (US)
    Pages (from-to)L118-L129
    JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
    Volume305
    Issue number2
    DOIs
    StatePublished - Jul 15 2013

    Keywords

    • Bronchoalveolar lavage fluid
    • Forced oscillation technique
    • Inflammation
    • Interleukin-6
    • Macrophage

    ASJC Scopus subject areas

    • Physiology
    • Pulmonary and Respiratory Medicine
    • Physiology (medical)
    • Cell Biology

    Fingerprint Dive into the research topics of 'Endogenous osteopontin promotes ozone-induced neutrophil recruitment to the lungs and airway hyperresponsiveness to methacholine'. Together they form a unique fingerprint.

  • Cite this

    Barreno, R. X., Richards, J. B., Schneider, D. J., Cromar, K. R., Nadas, A. J., Hernandez, C. B., Hallberg, L. M., Price, R. E., Hashmi, S. S., Blackburn, M. R., Haque, I. U., & Johnston, R. A. (2013). Endogenous osteopontin promotes ozone-induced neutrophil recruitment to the lungs and airway hyperresponsiveness to methacholine. American Journal of Physiology - Lung Cellular and Molecular Physiology, 305(2), L118-L129. https://doi.org/10.1152/ajplung.00080.2013