Severity of elastase-induced emphysema is decreased in tumor necrosis factor-alpha and interleukin-1beta receptor-deficient mice.
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) microm [mean(SE)]. For wild-type elastase-treated mice, Lm was 81(6) microm at 21 days versus 52(5) microm 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) microm 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-1beta, 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.
Lucey
Edgar C
EC
The Pulmonary Center, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts 02118, USA.
Keane
Joseph
J
Kuang
Ping-Ping
PP
Snider
Gordon L
GL
Goldstein
Ronald H
RH
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D018450:Disease Progression; D004646:Emphysema / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D010196:Pancreatic Elastase / Q000633:toxicity*; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012016:Reference Values
D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D010196:Pancreatic Elastase