Bleomycin-induced pulmonary fibrosis in hamsters: effect of neutrophil depletion on lung collagen synthesis.

Abstract

The development of pulmonary fibrosis in hamsters after the intratracheal instillation of bleomycin is attended by exudation of polymorphonuclear leukocytes (PMNs), but the function of these cells is unknown. In this study, we examined the effect of PMN depletion on lung collagen synthetic rate in bleomycin-treated hamsters. Antiserum to hamster PMNs was produced in rabbits and injected intraperitoneally into hamsters on the fourth through seventh days after intratracheal instillation of bleomycin or saline. Control animals received either normal rabbit serum (NRS) or no serum. Anti-PMN serum (APS) significantly reduced PMN exudation after bleomycin treatment through the eighth day (p less than 0.01). Collagen synthetic rate measured in lung explant cultures was increased in all bleomycin-treated groups compared with that in the saline injected control group (p less than 0.005). Collagen synthesis was greater in neutrophil-depleted bleomycin-treated hamsters than in bleomycin-treated animals receiving NRS or no serum on Days 8 (p less than 0.01) and 12 (p less than 0.05). In APS-treated hamsters, the proportion of protein synthesis directed toward collagen synthesis was increased above other bleomycin-treated groups, suggesting that collagen synthesis is selectively increased in neutrophil-depleted hamsters with bleomycin-induced pulmonary fibrosis.