Secretion of Epidermal Growth Factor-Like Molecular Species by Lung Parenchymal Macrophages: Induction by Interferon-γ

Abstract

A population of cells enriched for pulmonary interstitial macrophages was obtained by differential adherence of lung parenchymal cells released by dissociation with trypsin. These cells secreted a molecule or molecules that bound to epidermal growth factor (EGF) receptors expressed on pulmonary fibroblasts. Secretion was reprodudbly stimulated by exposure of the macrophages to interferon-y. Binding to EGF receptors could be blocked by a polyclonal antibody to EGF. It could also be partially blocked by incubation with heparin, suggesting that at least a component of the activity might be due to a member of the heparin-binding subgroup of the EGF family of growth factors. Because pulmonary fibrosis is consistently associated with inflammatory accumulation of activated T-lymphocytes, induction by interferon-y of growth factor secretion by macrophages could have pathoge-netic importance. We speculate that similar cellular interactions may play a role in the progression of other chronic inflammatory lesions to fibrosis.

Key Words:

• interstitial macrophages
• pulmonary fibrosis
• epidermal growth factor
• heparin-bindmg growth factors
• macrophage activation
• interferon-γ