title: Prolonged injury and altered lung function after ozone inhalation in mice with chronic lung inflammation.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Groves
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gow
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Massa
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Laskin
authors.forename: Debra L
authors.initials: DL
authors.lastname: Laskin
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D004548:Elasticity; D019570:Inhalation Exposure; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D055370:Lung Injury / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism; D010126:Ozone / Q000009:adverse effects*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism; D012129:Respiratory Function Tests
chemical_list: D000393:Air Pollutants; D009589:Nitrogen Oxides; D037663:Pulmonary Surfactant-Associated Protein D; D010126:Ozone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse