Prolonged injury and altered lung function after ozone inhalation in mice with chronic lung inflammation

Angela M. Groves, Andrew J. Gow, Christopher B. Massa, Jeffrey D. Laskin, Debra L. Laskin

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Surfactant protein-D (Sftpd) is a pulmonary collectin important in down-regulating macrophage inflammatory responses. In these experiments, we analyzed the effects of chronic macrophage inflammation attributable to loss of Sftpd on the persistence of ozone-induced injury, macrophage activation, and altered functioning in the lung. Wild-type (Sftpd+/+) and Sftpd -/- mice (aged 8 wk) were exposed to air or ozone (0.8 parts per million, 3 h). Bronchoalveolar lavage (BAL) fluid and tissue were collected 72 hours later. In Sftpd-/- mice, but not Sftpd+/+ mice, increased BAL protein and nitrogen oxides were observed after ozone inhalation, indicating prolonged lung injury and oxidative stress. Increased numbers of macrophages were also present in BAL fluid and in histologic sections from Sftpd-/- mice. These cells were enlarged and foamy, suggesting that they were activated. This conclusion was supported by findings of increased BAL chemotactic activity, and increased expression of inducible nitric oxide synthase in lung macrophages. In both Sftpd+/+ and Sftpd -/- mice, inhalation of ozone was associated with functional alterations in the lung. Although these alterations were limited to central airway mechanics in Sftpd+/+mice, both central airway and parenchymal mechanics were modified by ozone exposure in Sftpd-/- mice. The most notable changes were evident in resistance and elastance spectra and baseline lung function, and in lung responsiveness to changes in positive end-expiratory pressure. These data demonstrate that a loss of Sftpd is associated with prolonged lung injury, oxidative stress, and macrophage accumulation and activation in response to ozone, and with more extensive functional changes consistent with the loss of parenchymal integrity.

Original languageEnglish (US)
Pages (from-to)776-783
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume47
Issue number6
DOIs
StatePublished - Dec 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Keywords

  • Lung function
  • Macrophages
  • Ozone
  • Surfactant protein-D
  • iNOS

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