Age-related increases in ozone-induced injury and altered pulmonary mechanics in mice with progressive lung inflammation
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Authors: Groves, Angela M.; Gow, Andrew J.; Massa, Christopher B.; Hall, LeRoy; Laskin, Jeffrey D.; Laskin, Debra L.
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.
Serum-surfactant SP-D correlates inversely to lung function in cystic fibrosis
JOURNAL OF CYSTIC FIBROSIS
Authors: Olesen, Hanne Vebert; Holmskov, Uffe; Schiotz, Peter Oluf; Sorensen, Grith Lykke
Abstract
Background: Cystic fibrosis (CF) affects the lungs causing infections and inflammation. Surfactant protein D (SP-D) is an innate defense lectin primarily secreted in the lungs. We investigated the influence of the SP-D Met11Thr polymorphism on CF lung function; and serum SP-D as a marker for CF lung disease. Methods: For 107 CF patients (73 children, and 34 adults) serum SP-D and SP-D Met11Thr genotype were available. Leukocyte count was obtained for a subset of patients. Lung function was measured as forced expiratory volume in one second (FEV-1). Results: Serum SP-D was increased in CF patients compared to healthy controls, positively correlated to leukocyte count, and negatively conelated to FEV-1. We found no correlation between SP-D Met11Thr genotype and FEV-1, and we found corresponding genotype frequencies in CF patients and in healthy controls. Conclusion: Serum SP-D in CF patients was increased in parallel with leukocyte count and with reduced FEV-1 and may constitute an alternative biomarker for lung disease, in the clinical setting and in research. (C) 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.