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Human monocyte-derived growth factor(s) for mesenchymal cells: activation of secretion by endotoxin and concanavalin
Abstract:
Cultured peritoneal macrophages have previously been shown to release a potent mitogen for mesenchymal cells. Peritoneal macrophages are derived from peripheral blood monocytes, one of the principal inflammatory cells associated with numerous tissue responses to injury. Cultured human monocytes can be activated by endotoxin or concanavalin A to secrete a potent growth factor(s) that is active on human smooth muscle cells, human fibroblasts and 3T3 cells. The optimal conditions for activation of monocyte release of this monocyte derived growth factor(s) MDGF) were to expose 5-day-old monocyte cultures (initially plated at 6.8 X 10(5) cells/ml medium) to 10 microgram/ml endotoxin or 6 microgram/ml concanavalin A for approximately 20 hr. Monocytes can secrete MDGF into serum-free medium supplemented with 0.15% bovine serum albumin, MDGF stimulates both DNA synthesis and increase in cell number and is trypsin-sensitive, heat labile and nondialyzable. The relationship of MDGF to other monocyte products and its potential importance in wound repair and atherogenesis are discussed.
Insights
Human monocytes release a potent monocyte-derived growth factor (MDGF) that stimulates mesenchymal cell proliferation. This growth factor plays a key role in tissue repair and the development of atherosclerosis.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Cultured peritoneal macrophages secrete a mitogen for mesenchymal cells.
- Peritoneal macrophages originate from peripheral blood monocytes, key inflammatory cells involved in tissue repair.
- Cultured human monocytes, when activated, release potent growth factors.
Purpose of the Study:
- To investigate the activation conditions for monocyte release of monocyte-derived growth factors (MDGF).
- To characterize the properties of MDGF and its effects on target cells.
- To discuss the potential role of MDGF in wound repair and atherogenesis.
Main Methods:
- Culturing human monocytes for 5 days.
- Activating monocytes with endotoxin (10 µg/ml) or concanavalin A (6 µg/ml) for 20 hours.
- Collecting MDGF secreted into serum-free medium with 0.15% bovine serum albumin.
Main Results:
- Optimal MDGF release occurred under specific endotoxin or concanavalin A concentrations and incubation times.
- MDGF stimulates DNA synthesis and cell number increase in human smooth muscle cells, fibroblasts, and 3T3 cells.
- MDGF is trypsin-sensitive, heat-labile, and nondialyzable.
Conclusions:
- Human monocytes secrete a potent MDGF upon activation.
- MDGF exhibits characteristics of a protein growth factor.
- MDGF may be significant in wound healing and the pathogenesis of atherosclerosis.
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