Prolonged Injury and Altered Lung Function after Ozone Inhalation in Mice with Chronic Lung Inflammation

Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, New Jersey, United States.
American Journal of Respiratory Cell and Molecular Biology (Impact Factor: 3.99). 08/2012; 47(6). DOI: 10.1165/rcmb.2011-0433OC
Source: PubMed


Surfactant protein-D (Sftpd) is a pulmonary collectin important in down regulating macrophage inflammatory responses. In these studies we analyzed the effects of chronic macrophage inflammation due 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 (8 wk) were exposed to air or ozone (0.8 ppm, 3 h). Bronchoalveolar lavage fluid (BAL) and tissue were collected 72 h later. In Sftpd-/- mice, but not Sftpd+/+ mice, increased BAL protein and nitrogen oxides were observed following ozone inhalation indicating prolonged lung injury and oxidative stress. Increased numbers of macrophages were also present in BAL and in histologic sections from Sftpd-/- mice. These cells were enlarged and foamy suggesting that they are activated. This is 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. Whereas this was limited to central airway mechanics in Sftpd+/+ mice, both central airway and parenchymal mechanics were modified by ozone exposure in Sftpd-/- mice. Most notable changes were in resistance and elastance spectra and baseline lung functioning, in lung responsiveness to changes in positive end-expiratory pressure. These data demonstrate that loss of Sftpd is associated with prolonged lung injury, oxidative stress and macrophage accumulation and activation in response to ozone, and more extensive functional changes consistent with the loss of parenchymal integrity.

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