Thrombin Augments Vascular Cell-dependent Migration of Human Mast Cells: Role of MGF

Mehrdad Baghestanian; Roland Hofbauer; Hans G Kress; Johann Wojta; Astrid Fabry; Bernd R Binder; Christoph Kaun; Michael R Müller; Mohammad R Mehrabi; Stylianos Kapiotis; Gürkan Sengoelge; Minoo Ghannadan; Klaus Lechner; Peter Valent

doi:10.1055/s-0038-1656008

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 77(03): 577-584
DOI: 10.1055/s-0038-1656008

Vessel Wall

Schattauer GmbH Stuttgart

Thrombin Augments Vascular Cell-dependent Migration of Human Mast Cells: Role of MGF

Mehrdad Baghestanian

¹The Dept. of Internal Medicine I, Div. of Hematology, The University of Vienna, Austria

,

Roland Hofbauer

²The Dept. of Anaesthesiology and Gen. Intensive Care Med B, The University of Vienna, Austria

,

Hans G Kress

²The Dept. of Anaesthesiology and Gen. Intensive Care Med B, The University of Vienna, Austria

,

Johann Wojta

³The Inst. of Physiology, The University of Vienna, Austria

,

Astrid Fabry

³The Inst. of Physiology, The University of Vienna, Austria

,

Bernd R Binder

³The Inst. of Physiology, The University of Vienna, Austria

,

Christoph Kaun

³The Inst. of Physiology, The University of Vienna, Austria

,

Michael R Müller

⁴The Dept. of Surgery II, The University of Vienna, Austria

,

Mohammad R Mehrabi

⁵The Dept. of Internal Medicine II, Div. of Cardiology, The University of Vienna, Austria

,

Stylianos Kapiotis

⁶The Clinical Inst, of Med. Chem. Lab, The University of Vienna, Austria

,

Gürkan Sengoelge

⁷The Department of Internal Medicine III, Div. of Nephrology, The University of Vienna, Austria

,

Minoo Ghannadan

¹The Dept. of Internal Medicine I, Div. of Hematology, The University of Vienna, Austria

,

Klaus Lechner

¹The Dept. of Internal Medicine I, Div. of Hematology, The University of Vienna, Austria

,

Peter Valent

¹The Dept. of Internal Medicine I, Div. of Hematology, The University of Vienna, Austria

› Author Affiliations

Abstract

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Summary

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.

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References

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