期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 305, 期 8, 页码 L555-L568出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00027.2013
关键词
ozone; macrophages; aging; emphysema; surfactant protein D
资金
- National Institute of Health [R01ES004738, R01CA132624, R01HL086621, U54AR055073, P30ES005022, T32ES007148]
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.
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