The role of soluble factors in bleomycin-induced pulmonary fibrosis.

Endotracheal administration of bleomycin causes pulmonary fibrosis characterized by increased collagen synthesis and deposition. Incubation of normal lung mince with neutral salt soluble extracts of lungs from normal and bleomycin-treated rats caused a dose-dependent inhibition of collagen and noncollagenous protein synthesis. Bleomycin-treated lung extracts, however, were significantly less effective in such inhibition when compared with normal lung extracts. This inhibitory activity was not diminished by dialysis in tubing with nominal molecular weight cutoff of 10,000 but was destroyed by heat (70 C) and trypsin digestion. This inhibitory activity could not be ascribed to residual serum or bleomycin in the lung extracts. Fractionation on Sephacryl S-200 (Pharmacia, Piscataway, NJ) showed inhibitory activity to be heterogeneous with Mr (apparent molecular weight) greater than 100,000. Extracts from spleen showed similar inhibitory activity but showed no difference in intensity between normal and bleomycin-treated spleen. These data suggest that loss or decrease in production of lung inhibitory regulatory factors is partly responsible for the noted increase in collagen production and deposition in bleomycin-induced pulmonary fibrosis.