Enhanced production of an EGF-like growth factor by parenchymal macrophages following bleomycin-induced pulmonary injury

The secretion of molecular species related to epidermal growth factor (EGF) by pulmonary alveolar and parenchymal macrophages was investigated in an experimental model of pulmonary fibrosis in mice. Macrophages were isolated from cells obtained by bronchoalveolar lavage or by enzymatic disaggregation of lung tissue at intervals following induction of pulmonary injury by intratracheal injection of bleomycin. Production of EGF receptor-binding activity by these cells and concentrations of this activity in bronchoalveolar lavage fluid were measured using a radioreceptor assay. Following short-term culture under serum-free conditions, there was significantly increased production of EGF receptor-binding activity by parenchymal macrophages, which was demnonstrable at 1 and 2 weeks after administration of bleomycin to susceptible C57BL/6 mice. The activity exhibited affinity for heparin and was completely blocked by an antibody to EGF. There was no such increase in production of receptor-binding activity by alveolar macrophages or in the concentration of activity in lavage fluids. Nor was there any significant increase in production of EGF receptor-binding activity by parenchymal macrophages from bleomycin-resistant BALB/c mice. These results imply that selective activation of interstitial macrophages to secrete an EGF-like growth factor may contribute to the development of pulmonary fibrosis.