BLEOMYCIN INJURY OF THE LUNG IN A MAST-CELL-DEFICIENT MODEL

Lung mast cell hyperplasia and fibrosis is induced by bleomycin lung i njury. The role of the mast cell in this process of injury and resulta nt fibrosis is unclear. Mutant mi/mi mice, profoundly mast-cell-defici ent, were treated with intraperitoneal bleomycin and demonstrated mini mal acute inflammatory and chronic fibrotic responses. Lung histamine values determined at 14 and 42 days after bleomycin injury in mi/mi mi ce were not increased compared to untreated mi/mi animals. However, lu ng histamine levels in normal mice demonstrated a 300% increase over c ontrols on Day 14 after bleomycin injury, and then returned to baselin e by Day 42. The mi/mi BAL cell recovery at 2 weeks after injury and l ung hydroxyproline levels at 4 weeks after injury were not altered fro m baseline. The normal litter mates, in contrast, demonstrated signifi cant increases compared to controls in both of these parameters (p < 0 .01, p < 0.04). Although the mi/mi mouse is also deficient in basophil s, natural killer cells and functional osteoclasts, there is no eviden ce of lowered pulmonary defense mechanism and neutrophils and alveolar macrophages are present in normal numbers. This investigation support s the hypothesis that the mast cell contributes to bleomycin-induced l ung injury and fibrosis.