SECRETION OF EPIDERMAL GROWTH FACTOR-LIKE MOLECULAR-SPECIES BY LUNG PARENCHYMAL MACROPHAGES - INDUCTION BY INTERFERON-GAMMA

A population of cells enriched for pulmonary interstitial macrophages was obtained by differential adherence of lung parenchymal cells relea sed by dissociation with trypsin. These cells secreted a molecule or m olecules that bound to epidermal growth factor (EGF) receptors express ed on pulmonary fibroblasts. Secretion was reproducibly stimulated by exposure of the macrophages to interferon-gamma. Binding to EGF recept ors could be blocked by a polyclonal antibody to EGF. It could also be partially blocked by incubation with heparin, suggesting that at leas t a component of the activity might be due to a member of the heparin- binding subgroup of the EGF family of growth factors. Because pulmonar y fibrosis is consistently associated with inflammatory accumulation o f activated T-lymphocytes, induction by interferon-gamma of growth fac tor secretion by macrophages could have pathogenetic importance. We sp eculate that similar cellular interactions may play a role in the prog ression of other chronic inflammatory lesions to fibrosis.