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

@entity568 @entity2041 @entity1505 @entity2415 @entity329 @entity1129 @entity3426 @entity35 @entity647
Elastase intratracheal instillation induces @entity2415 in rodents. However, @entity329 develop more severe @entity2415 than @entity35 . 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. @entity35 and @entity329 received a single dose of pancreatic elastase (0.55 U/100 g body wt) to study @entity647 biomarkers. Using serum, lung, and bronchoalveolar lavage fluid (BALF) samples, we evaluated changes in alveolar-capillary permeability, alpha 1-antitrypsin (a(1)- @entity1129 ) concentration and activity, @entity2041 content, and proinflammatory cytokines. @entity35 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 a(1)- @entity1129 concentration in @entity35 and only a 7-fold increase in hamsters (P < 0.001), with [a(1)- @entity1129 -elastase] complexes only in @entity35 , suggesting differences in antiprotease function. This was confirmed by the a(1)- @entity1129 bioassay showing 20-fold increase in a(1)- @entity1129 activity in @entity35 and only twofold increase in hamsters (P < 0.001). In @entity35 , results were preceded by a 3-, 60-, and 20-fold increase in @entity568 , @entity3426 , and @entity1505 respectively (P < 0.001). In hamsters, only @entity3426 and @entity1505 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 a(1)- @entity1129 were the most significant components differing among species and could account for differences in susceptibility to elastase.
