title: Differences in acute lung response to elastase instillation in two rodent species may determine differences in severity of emphysema development.
abstract: 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 (α(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 α(1)-AT concentration in rats and only a 7-fold increase in hamsters (P < 0.001), with [α(1)-AT-elastase] complexes only in rats, suggesting differences in antiprotease function. This was confirmed by the α(1)-AT bioassay showing 20-fold increase in α(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-1β, and TNF-α respectively (P < 0.001). In hamsters, only IL-1β and TNF-α 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 α(1)-AT were the most significant components differing among species and could account for differences in susceptibility to elastase.
authors.affiliation: Dept. of Respiratory Diseases, Pontificia Universidad Católica de Chile, Marcoleta 350, piso 1, Santiago, Chile.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vecchiola
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: de la Llera
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ramírez
authors.forename: Pablo
authors.initials: P
authors.lastname: Olmos
authors.forename: Cristobal I
authors.initials: CI
authors.lastname: Herrera
authors.forename: Gisella
authors.initials: G
authors.lastname: Borzone
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D007267:Injections; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008647:Mesocricetus; D010196:Pancreatic Elastase / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013045:Species Specificity; D000515:alpha 1-Antitrypsin / Q000378:metabolism
chemical_list: D016207:Cytokines; D000515:alpha 1-Antitrypsin; D010196:Pancreatic Elastase; D005978:Glutathione