title: Age-related increases in ozone-induced injury and altered pulmonary mechanics in mice with progressive lung inflammation.
abstract: In these studies we determined whether progressive pulmonary inflammation associated with aging in surfactant protein D (Sftpd)-/- mice leads to an exacerbated response to ozone. In Sftpd-/- mice, but not wild-type (WT) mice, age-related increases in numbers of enlarged vacuolated macrophages were observed in the lung, along with alveolar wall rupture, type 2 cell hyperplasia, and increased bronchoalveolar lavage protein and cell content. Numbers of heme oxygenase+ macrophages also increased with age in Sftpd-/- mice, together with classically (iNOS+) and alternatively (mannose receptor+, YM-1+, or galectin-3+) activated macrophages. In both WT and Sftpd-/- mice, increasing age from 8 to 27 wk was associated with reduced lung stiffness, as reflected by decreases in resistance and elastance spectra; however, this response was reversed in 80-wk-old Sftpd-/- mice. Ozone exposure (0.8 ppm, 3 h) caused increases in lung pathology, alveolar epithelial barrier dysfunction, and numbers of iNOS+ macrophages in 8- and 27-wk-old Sftpd-/-, but not WT mice at 72 h postexposure. Conversely, increases in alternatively activated macrophages were observed in 8-wk-old WT mice following ozone exposure, but not in Sftpd-/- mice. Ozone also caused alterations in both airway and tissue mechanics in Sftpd-/- mice at 8 and 27 wk, but not at 80 wk. These data demonstrate that mild to moderate pulmonary inflammation results in increased sensitivity to ozone; however, in senescent mice, these responses are overwhelmed by the larger effects of age-related increases in baseline inflammation and lung injury.
authors.affiliation: Dept. of Pharmacology and Toxicology, Rutgers Univ., Ernest Mario School of Pharmacy, 160 Frelinghuysen Rd., Piscataway, NJ 08854 (laskin@eohsi.rutgers.edu.
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: LeRoy
authors.initials: L
authors.lastname: Hall
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Laskin
authors.forename: Debra L
authors.initials: DL
authors.lastname: Laskin
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D055370:Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008262:Macrophage Activation / Q000187:drug effects / Q000235:genetics; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010083:Oxidants, Photochemical / Q000009:adverse effects* / Q000494:pharmacology; D010126:Ozone / Q000009:adverse effects* / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors
chemical_list: D010083:Oxidants, Photochemical; D037663:Pulmonary Surfactant-Associated Protein D; D010126:Ozone
keywords: aging; emphysema; macrophages; ozone; surfactant protein D