Imatinib reduces hydroxyproline content and prevents histopathologic changes in BLM-treated lungs. (A) Twenty-eight days after intratracheal instillation of BLM or saline, mice were sacrificed (control, n = 12; BLM, n = 15; BLM plus imatinib, n = 14; imatinib, n = 8). The left lung of each animal was used for hydroxyproline assay as described in Methods and previously (52). *P < 0.05 vs. BLM mice receiving imatinib. There was no significant difference (P > 0.05) among control, BLM plus imatinib, and imatinib groups. (B) Mice were treated as in A. The right lung was sectioned and stained with H&E or Masson’s trichrome to visualize collagen. Representative images are shown at ×10 phase. (C) A morphologic score (44) was assigned in a blinded fashion to H&E-stained samples. Zero indicates no fibrosis, 1 indicates occasional small subpleural foci, 2 indicates interalveolar septal thickening and subpleural foci, and 3 indicates continuous interalveolar and subpleural fibrosis. There was no significant difference among the control, BLM plus imatinib, and imatinib groups. (D) Mice were treated as described for A. Immediately prior to explantation trachea were cannulated and lavaged with a total of 10 ml 0.9 normal saline. The collected fluid was centrifuged, and the cell differential was determined. Gray bars indicate percent macrophages, while red and green reflect polymorphonuclear cells and lymphocytes, respectively. Error bars indicate the SE of measurement between samples within the same group.