THROMBIN INDUCED MAST CELL CHEMOTAXIS MIGHT PLAY AN ESSENTIAL ROLE IN THROMBOSIS:

S415 BACKGROUND: Recent data suggest that auricular thrombosis is associated with accumulation of mast cell (MC) chemotaxis in the upper endocardium. The aim of the current study the role of vascular cells, thrombin-activation and mast cell growth factor (MGF), in mast cell migration was analyzed. MATERIALS: Cultured human auricular endocardial cells (HAUEC), umbilical vein endothelial cells (HUVEC) and uterine-(HUTMEC) and skin-derived (SMEC) 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 mast cell line) against vascular cells (supernatants) measured. RESULTS: Supernatants (24h) 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 cells [291 +/- 34%]; vs HAUEC: 9703 +/- 1506 cells [320 +/- 49.8%]; vs. HUTMEC: 8950 +/- 1857 cells [295 +/- 61.4%]; vs. HSMEC: 9965 +/- 2018 cells [329 +/- 66.7%]; vs HUVEC: 9487 +/- 1402 cells [313 +/- 46.4%] as well as in primary lung mast cells. Thrombin activation (5 U/ml, 12h) of vascular cells led to an augmentation of the directed migration of mast cells as well as to a hirudin-sensitive increase in MGF synthesis and release. Moreover, a blocking anti-MGF antibody was found to inhibit vascular cell-dependent migration. CONCLUSION: These data show that endocardial and other vascular cells can induce migration of human mast cells. This mast cell chemotactic signal of the vasculature is associated with expression and release of mast cell growth factor, augmentable by thrombin, and may play a role in (auricular) thrombosis.