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Mast cell modulation of macrophage procoagulant activity and TNF production
A P Dackiw1, A B Nathens, M B Ribeiro
1Department of Surgery, University of Toronto, Canada.
Abstract:
The expression of surface procoagulants by macrophages represents an important mechanism underlying local fibrin deposition at sites of extravascular inflammation. Mast cells by virtue of their perivascular location are in a potent position to influence the inflammatory process. The present studies investigated the role of the mast cell in the generation of macrophage procoagulant activity (PCA) and tumor necrosis factor (TNF) production. Mast cell lysates caused a marked induction of macrophage PCA (dose and time dependent) and TNF release while whole mast cells had little effect. This effect was prevented by the tyrosine kinase inhibitor herbimycin. At the molecular level, Northern blot analysis revealed marked induction of the murine macrophage tissue factor transcript in response to incubation with mast cell lysate compared to control. These studies thus suggest that mast cell-macrophage interactions promote macrophage-mediated fibrin deposition and TNF release and that this effect is in part mediated via induction of tyrosine phosphorylation. These observations suggest novel mechanisms of involvement of the mast cell in the inflammatory microenvironment and macrophage activation.
Insights
Mast cell components activate macrophages to produce procoagulant activity (PCA) and tumor necrosis factor (TNF). This interaction, mediated by tyrosine phosphorylation, influences fibrin deposition in inflammation.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- Macrophages express surface procoagulants, crucial for fibrin deposition in inflammation.
- Mast cells, due to their location, significantly impact inflammatory processes.
Purpose of the Study:
- To investigate the role of mast cells in macrophage procoagulant activity (PCA) and tumor necrosis factor (TNF) production.
- To elucidate the molecular mechanisms behind mast cell-macrophage interactions in inflammation.
Main Methods:
- Incubation of macrophages with mast cell lysates and whole mast cells.
- Treatment with tyrosine kinase inhibitor herbimycin.
- Northern blot analysis to assess tissue factor transcript levels.
Main Results:
- Mast cell lysates significantly induced macrophage PCA and TNF release in a dose- and time-dependent manner.
- Whole mast cells showed minimal effect on PCA and TNF production.
- The induction of PCA and TNF by mast cell lysates was inhibited by herbimycin.
- Northern blot analysis revealed increased murine macrophage tissue factor transcript levels upon exposure to mast cell lysate.
Conclusions:
- Mast cell-macrophage interactions promote macrophage-mediated fibrin deposition and TNF release.
- Tyrosine phosphorylation plays a key role in mediating these mast cell effects.
- These findings reveal novel mechanisms of mast cell involvement in the inflammatory microenvironment and macrophage activation.