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Phorbol ester stimulates macrophage invasion of fibrin matrices
1Institute of Histology and Embryology, University of Geneva Medical School, Switzerland.
Abstract:
Macrophages migrate through a fibrin-rich extracellular matrix in chronic inflammation, wound healing, and other pathophysiological processes. To investigate the factors that might influence the ability of mononuclear phagocytes to invade fibrin matrices, we cultured macrophage-like P388D1 cells as well as resident and thioglycollate-elicited mouse peritoneal macrophages on three-dimensional fibrin gels, and we examined the effect of agents known to stimulate a variety of macrophage functions, including the production of fibrinolytic enzymes. Cells grown on fibrin gels under control conditions, as well as cells treated with either bacterial lipopolysaccharide or concanavalin A, remained confined to the gel surface. In contrast, the tumor promoter 4 beta-phorbol 12-myristate 13-acetate (PMA) induced both P388D1 cells and peritoneal macrophages to invade the underlying fibrin matrix. The invasive behavior of PMA-treated P388D1 cells was not affected by protease inhibitors of various specificities. These results demonstrate that certain exogenous signals can profoundly modify the ability of macrophages to migrate through fibrin matrices.
Insights
Certain external signals, like 4beta-phorbol 12-myristate 13-acetate (PMA), enable macrophages to invade fibrin matrices. Other agents, including lipopolysaccharide, do not promote this crucial cell migration.
Area of Science:
- Cell Biology
- Immunology
- Extracellular Matrix Research
Background:
- Macrophages are crucial immune cells that navigate complex extracellular matrices.
- Fibrin matrices are prevalent in inflammatory and wound healing processes.
- Understanding macrophage migration through fibrin is key to various pathophysiological conditions.
Purpose of the Study:
- To investigate factors influencing macrophage invasion of fibrin matrices.
- To determine how specific agents affect macrophage-PMA interaction with fibrin.
- To explore the role of fibrinolytic enzymes in macrophage matrix invasion.
Main Methods:
- Culturing macrophage-like P388D1 cells and primary mouse macrophages on 3D fibrin gels.
- Treating cells with bacterial lipopolysaccharide, concanavalin A, and 4beta-phorbol 12-myristate 13-acetate (PMA).
- Observing and analyzing cell behavior and invasion patterns using microscopy and protease inhibitor assays.
Main Results:
- Macrophages cultured on fibrin gels did not invade the matrix under control conditions or when treated with lipopolysaccharide or concanavalin A.
- 4beta-phorbol 12-myristate 13-acetate (PMA) significantly induced invasion of the fibrin matrix by both P388D1 cells and primary macrophages.
- The invasive behavior induced by PMA was independent of protease activity, as protease inhibitors did not alter it.
Conclusions:
- Exogenous signals, particularly PMA, can profoundly influence macrophage migratory and invasive capabilities within fibrin matrices.
- Macrophage invasion of fibrin is a regulated process that can be triggered by specific external stimuli.
- This finding has implications for understanding inflammatory diseases and tissue repair.