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Secretion of epidermal growth factor-like molecular species by lung parenchymal macrophages: induction by
1School of Pathology, University of New South Wales, Kensington, Australia.
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 reproducibly stimulated by exposure of the macrophages to interferon-gamma. 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-gamma of growth factor secretion by macrophages could have pathogenetic importance. We speculate that similar cellular interactions may play a role in the progression of other chronic inflammatory lesions to fibrosis.
Insights
Pulmonary macrophages stimulated by interferon-gamma secrete factors that bind to epidermal growth factor receptors on lung fibroblasts, potentially contributing to fibrosis. This highlights a role for macrophage-derived growth factors in chronic inflammatory diseases.
Area of Science:
- Cell biology
- Immunology
- Pulmonary medicine
Background:
- Pulmonary fibrosis is associated with inflammation and T-lymphocyte accumulation.
- Macrophages play a role in inflammatory processes within the lung.
Purpose of the Study:
- To investigate the interaction between pulmonary interstitial macrophages and lung fibroblasts.
- To identify molecules secreted by macrophages that affect fibroblast behavior.
Main Methods:
- Pulmonary interstitial macrophages were isolated using differential adherence.
- Macrophage secretion was stimulated with interferon-gamma.
- Binding of secreted molecules to epidermal growth factor (EGF) receptors on fibroblasts was assessed using antibody and heparin inhibition.
Main Results:
- Isolated macrophages secreted factors that bound to EGF receptors on pulmonary fibroblasts.
- Interferon-gamma stimulation reproducibly increased this secretion.
- Binding was inhibited by anti-EGF antibody and partially by heparin, suggesting involvement of heparin-binding EGF-like growth factors.
Conclusions:
- Macrophages, when stimulated by interferon-gamma, release factors that interact with fibroblast EGF receptors.
- This macrophage-fibroblast interaction, mediated by growth factors, may be important in the pathogenesis of pulmonary fibrosis.
- Similar mechanisms could contribute to fibrosis in other chronic inflammatory conditions.