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Thrombin augments vascular cell-dependent migration of human mast cells: role of MGF
M Baghestanian1, R Hofbauer, H G Kress
1Dept. of Internal Medicine I, University of Vienna, Austria.
Abstract:
Recent data suggest that auricular thrombosis is associated with accumulation of mast cells (MC) in the upper endocardium (where usually no MC reside) and local expression of MGF (mast cell growth factor) (25). In this study, the role of vascular cells, thrombin-activation and MGF, in MC-migration was analyzed. For this purpose, cultured human auricular endocardial cells (HAUEC), umbilical vein endothelial cells (HUVEC) and uterine- (HUTMEC) and skin-derived (HSMEC) microvascular endothelial cells were exposed to thrombin or control medium, and the migration of primary tissue MC (lung, n = 6) and HMC-1 cells (human MC-line) against vascular cells (supernatants) measured. Supernatants (24 h) of unstimulated vascular cells (monolayers of endocardium or endothelium) as well as recombinant (rh) MGF induced a significant migratory response in HMC-1 (control: 3025 +/- 344 cells [100 +/- 11.4%] vs. MGF, 100 ng/ml: 8806 +/- 1019 [291 +/- 34%] vs. HAUEC: 9703 +/- 1506 [320.8 +/- 49.8%] vs. HUTMEC: 8950 +/- 1857 [295.9 +/- 61.4%] vs. HSMEC: 9965 +/- 2018 [329.4 +/- 66.7%] vs. HUVEC: 9487 +/- 1402 [313.6 +/- 46.4%], p < 0.05) as well as in primary lung MC. Thrombin-activation (5 U/ml, 12 h) of vascular cells led to an augmentation of the directed migration of MC as well as to a hirudin-sensitive increase in MGF synthesis and release. Moreover, a blocking anti-MGF antibody was found to inhibit MC-migration induced by unstimulated or thrombin-activated vascular cells. Together, these data show that endocardial and other vascular cells can induce migration of human MC. This MC-chemotactic signal of the vasculature is associated with expression and release of MGF, augmentable by thrombin, and may play a role in the pathophysiology of (auricular) thrombosis.
Insights
Vascular cells, including endocardial cells, attract mast cells (MC) via mast cell growth factor (MGF). Thrombin enhances this process, suggesting a role in auricular thrombosis.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Biology
Background:
- Auricular thrombosis is linked to mast cell (MC) accumulation in the endocardium.
- Local expression of mast cell growth factor (MGF) is observed in these cases.
Purpose of the Study:
- To investigate the role of vascular cells, thrombin activation, and MGF in mast cell migration.
- To analyze the chemotactic signals from vascular cells that influence mast cell movement.
Main Methods:
- Cultured human auricular endocardial cells (HAUEC), umbilical vein endothelial cells (HUVEC), and microvascular endothelial cells (HUTMEC, HSMEC) were used.
- Cells were exposed to thrombin or control medium.
- Migration of primary lung MC and HMC-1 cells towards vascular cell supernatants was measured.
Main Results:
- Supernatants from unstimulated vascular cells and recombinant MGF significantly induced migration of HMC-1 and primary lung MC.
- Thrombin activation of vascular cells augmented MC migration and increased MGF synthesis and release.
- A blocking anti-MGF antibody inhibited MC migration induced by both unstimulated and thrombin-activated vascular cells.
Conclusions:
- Endocardial and other vascular cells can induce human MC migration.
- This vascular-derived MC-chemotactic signal involves MGF expression and release, which is enhanced by thrombin.
- These findings suggest a potential role in the pathophysiology of auricular thrombosis.