Differences in acute lung response to elastase instillation in two rodent species may determine differences in severity of emphysema development
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Date
2011
Journal Title
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Publisher
AMER PHYSIOLOGICAL SOC
Abstract
Vecchiola A, de la Llera JF, Ramirez R, Olmos P, Herrera CI, Borzone G. Differences in acute lung response to elastase instillation in two rodent species may determine differences in severity of emphysema development. Am J Physiol Regul Integr Comp Physiol 301: R148-R158, 2011. First published April 13, 2011; doi:10.1152/ajpregu.00133.2011.-Elastase intratracheal instillation induces early emphysema in rodents. However, Syrian Golden hamsters develop more severe emphysema than Sprague-Dawley rats. We have reported species differences in oxidant/antioxidant balance modulating antiprotease function early after instillation. We now hypothesize that other components of the initial lung response to elastase might also be species-dependent. Sprague-Dawley rats and Syrian Golden hamsters received a single dose of pancreatic elastase (0.55 U/100 g body wt) to study acute lung injury biomarkers. Using serum, lung, and bronchoalveolar lavage fluid (BALF) samples, we evaluated changes in alveolar-capillary permeability, alpha 1-antitrypsin (alpha(1)-AT) concentration and activity, glutathione content, and proinflammatory cytokines. Rats showed a large increase in alveolar-capillary permeability and few hemorrhagic changes, whereas hamsters exhibited large hemorrhagic changes (P < 0.01) and mild transendothelial passage of proteins. Western blots showed a 30-fold increase in BALF alpha(1)-AT concentration in rats and only a 7-fold increase in hamsters (P < 0.001), with [alpha(1)-AT-elastase] complexes only in rats, suggesting differences in antiprotease function. This was confirmed by the alpha(1)-AT bioassay showing 20-fold increase in alpha(1)-AT activity in rats and only twofold increase in hamsters (P < 0.001). In rats, results were preceded by a 3-, 60-, and 20-fold increase in IL-6, IL-1 beta, and TNF-alpha respectively (P < 0.001). In hamsters, only IL-1 beta and TNF-alpha showed mild increases. All parameters studied were back to baseline by 4 days. In conclusion, several components of the initial lung response showed species differences. Cytokine release pattern and functional inhibition of alpha(1)-AT were the most significant components differing among species and could account for differences in susceptibility to elastase.
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Keywords
alpha(1)-antitrypsin, elastase, animal models, acute lung injury, hemorrhage, experimental, ACUTE-PHASE RESPONSE, RESPIRATORY-DISTRESS-SYNDROME, INDUCED PULMONARY-EMPHYSEMA, CIGARETTE-SMOKE, ALPHA(1)-PROTEINASE INHIBITOR, NEUTROPHIL ELASTASE, EPITHELIAL-CELLS, DESTRUCTION, INJURY, ALPHA