Repair of oxygen-induced lung injury in adult rats. The role of ornithine decarboxylase and polyamines

Abstract

We studied the repair of lung injury in adult rats exposed to 100% oxygen for 60 h, then placed in ambient air. Lung ornithine decarboxylase (ODC) activity and polyamine (putrescine, spermidine, and spermine) content during repair were correlated with changes in lung ultrastructure. The effect of difluoromethylornithine (DFMO), a selective Irreversible ODC inhibitor, was also studied; ODC activity increased to 25-fold baseline 2 days after injury and returned to normal by 7 days. Polyamine content increased to 3-fold baseline during the first 3 days. During the same period, the number of capillary endothelial cells and the capillary surface area almost doubled, and the number of type 2 epithelial cells increased 2.5-fold. The DFMO treatment lowered ODC activities below baseline, reduced the increase in polyamine content, and also reduced the morphometric parameters described above to only 60 to 70% of the values during normal repair. It also caused a significant decrease in the number of type 1 epithelial cells during repair, suggesting that deficient replacement by differentiating type 2 epithelial cells occurred. We conclude that marked changes in lung ODC activity and polyamine content occur during the repair of oxygen-induced injury to the lung and that selective inhibition of these changes adversely affects repair.