LUNG MONOCYTE CHEMOATTRACTANT PROTEIN-1 GENE-EXPRESSION IN BLEOMYCIN-INDUCED PULMONARY FIBROSIS

Recent studies indicate that monocyte chemoattractant protein-1 (MCP-1 ) may play an important role in pulmonary inflammation. In vitro studi es show that a number of cell types are capable of producing MCP-1. In this study, MCP-1 expression in lungs of rats with bleomycin (BLM)-in duced pulmonary fibrosis is examined to evaluate its cellular origin a nd potential role in pathogenesis. Lung fibrosis was induced in male F isher 344 rats by endotracheal injection on day 0. On selected days af ter injection, lungs were harvested for in situ and Northern hybridiza tion analyses for MCP-1 mRNA expression, immunochemical and histochemi cal analyses for MCP-1 protein expression, and identification of cell type. Northern analysis revealed significant elevation in lung MCP-1 m RNA expression beginning on day 3 post-BLM treatment, increasing to a peak on day 7, and then decreasing toward control levels after day 21. In situ hybridization combined with histochemical staining with chrom otrope 2R indicate that most of the cells expressing MCP-1 mRNA at the se time points are primarily eosinophils. A few scattered reactive fib roblasts, some mononuclear cells, epithelial cells, and cells of certa in blood vessel walls also express this mRNA. Increased MCP-1 protein expression also was found to be predominantly within and adjacent to e osinophils. The eosinophils expressing this mRNA were found predominan tly within areas of active fibrosis. The kinetics of increase in the n umber of cells expressing significant MCP-1 mRNA in lung sections para lleled that for MCP-1 mRNA expression, as assessed by Northern analysi s. These results, for the first time, demonstrate that MCP-1 is up-reg ulated significantly in this rat animal model, and that infiltrating e osinophils represent the major cellular source For this increased MCP- 1 expression.