Differences in acute lung response to elastase instillation in two rodent species may determine differences in severity of emphysema development

作者：Vecchiola Andrea; Francisco de la Llera Juan; Ramirez Rodrigo; Olmos Pablo; Herrera Cristobal I; Borzone Gisella^*

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2011, 301(1): R148-R158.

DOI：10.1152/ajpregu.00133.2011

• alpha(1)-antitrypsin
• elastase
• animal models
• acute lung injury
• hemorrhage
• experimental

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.

• 出版日期2011-7