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 (mannosereceptor+, YM-1 +, orgalectin-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.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Volume | 305 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 15 Oct 2013 |
| Externally published | Yes |
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Keywords
- Aging
- Emphysema
- Macrophages
- Ozone
- Surfactant protein D
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology
- Physiology
Cite this
Age-related increases in ozone-induced injury and altered pulmonary mechanics in mice with progressive lung inflammation. / Groves, Angela M.; Gow, Andrew J.; Massa, Christopher B.; Hall, Le Roy; Laskin, Jeffrey D.; Laskin, Debra L.
In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 305, No. 8, 15.10.2013.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Age-related increases in ozone-induced injury and altered pulmonary mechanics in mice with progressive lung inflammation
AU - Groves, Angela M.
AU - Gow, Andrew J.
AU - Massa, Christopher B.
AU - Hall, Le Roy
AU - Laskin, Jeffrey D.
AU - Laskin, Debra L.
PY - 2013/10/15
Y1 - 2013/10/15
N2 - 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 (mannosereceptor+, YM-1 +, orgalectin-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.
AB - 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 (mannosereceptor+, YM-1 +, orgalectin-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.
KW - Aging
KW - Emphysema
KW - Macrophages
KW - Ozone
KW - Surfactant protein D
UR - http://www.scopus.com/inward/record.url?scp=84885656135&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885656135&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00027.2013
DO - 10.1152/ajplung.00027.2013
M3 - Article
C2 - 23997172
AN - SCOPUS:84885656135
VL - 305
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
SN - 1040-0605
IS - 8
ER -