Severity of elastase-induced emphysema is decreased in tumor necrosis factor-α and interleukin-1β receptor-deficient mice

被引:132
作者
Lucey, EC
Keane, J
Kuang, PP
Snider, GL
Goldstein, RH
机构
[1] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA
[3] VA Boston Healthcare Syst, Boston, MA USA
关键词
D O I
10.1038/labinvest.3780397
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
A single intratracheal dose of porcine pancreatic elastase, which is cleared from the lung by 24 hours, was administered to wild-type, IL-1beta type 1 receptor-deficient, double TNF-alpha (type 1 and type 2) receptor-deficient, and combined TNF-alpha (type 1 receptor) plus IL-1beta receptor-deficient mice. The mean linear intercept (Lm) of saline-treated mice was 32(3) mum [mean(SE)]. For wild-type elastase-treated mice, Lm was 81(6) mum at 21 days versus 52(5) mum at 5 days after treatment, indicating that alveolar wall remodeling occurs long after the elastase injury. At 21 days, Lm values were 67(10), 62(3), and 39(5) gm in elastase-treated mice deficient in the IL-1beta receptor, double TNF-alpha receptors, and combined receptors, respectively. The level of apoptosis assessed by a terminal deoxynucleotidyl transferase-catalyzed in situ nick end-labeling assay was increased at 5 days after elastase treatment and was markedly and similarly attenuated in the IL-10, the double TNF-alpha, and the combined receptor-deficient mice. Our results indicate that inflammatory mediators exacerbate elastase-induced emphysema. We estimate that in the combined TNF-alpha + IL-1beta receptor-deficient mice, inflammation accounts for about 80% of the emphysema that develops after elastase treatment; decreased apoptosis of lung cells likely contributes to decreased severity of emphysema.
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页码:79 / 85
页数:7
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