Mast cells (MCs) are immunoregulatory and inflammatory tissue cells preferentially located around blood vessels. Since endothelial cells have been suggested to regulate MC functions, we analyzed MC–endothelial cell interactions in vitro by performing coculture experiments with purified human intestinal MCs and human umbilical vein endothelial cells (HUVECs). We found that HUVECs provide signals allowing MCs to survive for at least 3 wk and to proliferate without addition of cytokines; otherwise all MCs died. HUVEC-dependent MC proliferation was more pronounced than that induced by stem cell factor (SCF), known to act as an MC growth factor both in vitro and in vivo. After coculture with HUVECs, most MCs were of the tryptase and chymase double-positive phenotype (MCTC). Transwell experiments suggested that the HUVECs' effects on MCs are not mediated by soluble factors. HUVEC-dependent MC adhesion and proliferation were inhibited by neutralizing antibodies directed against SCF and vascular cell adhesion molecule (VCAM)-1 expressed on HUVECs, and c-kit and very late antigen 4 (VLA-4) on MCs. The data suggest that two mechanisms (membrane-bound SCF/c-kit and VCAM-1/VLA-4) are involved in human MC–endothelial cell interactions. In conclusion, our study provides evidence that endothelial cells regulate MC survival and preferentially support human MCTC development.
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18 September 2000
Article|
September 11 2000
Human Endothelial Cells Regulate Survival and Proliferation of Human Mast Cells
Claudia T. Mierke,
Claudia T. Mierke
aDepartment of Gastroenterology and Hepatology, Medical School Hannover, D-30625 Hannover, Germany
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Matthias Ballmaier,
Matthias Ballmaier
cDepartment of Pediatric Hematology and Oncology, Medical School Hannover, D-30625 Hannover, Germany
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Uwe Werner,
Uwe Werner
bDepartment of Visceral and Transplant Surgery, Medical School Hannover, D-30625 Hannover, Germany
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Michael P. Manns,
Michael P. Manns
aDepartment of Gastroenterology and Hepatology, Medical School Hannover, D-30625 Hannover, Germany
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Karl Welte,
Karl Welte
cDepartment of Pediatric Hematology and Oncology, Medical School Hannover, D-30625 Hannover, Germany
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Stephan C. Bischoff
Stephan C. Bischoff
aDepartment of Gastroenterology and Hepatology, Medical School Hannover, D-30625 Hannover, Germany
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Claudia T. Mierke
aDepartment of Gastroenterology and Hepatology, Medical School Hannover, D-30625 Hannover, Germany
Matthias Ballmaier
cDepartment of Pediatric Hematology and Oncology, Medical School Hannover, D-30625 Hannover, Germany
Uwe Werner
bDepartment of Visceral and Transplant Surgery, Medical School Hannover, D-30625 Hannover, Germany
Michael P. Manns
aDepartment of Gastroenterology and Hepatology, Medical School Hannover, D-30625 Hannover, Germany
Karl Welte
cDepartment of Pediatric Hematology and Oncology, Medical School Hannover, D-30625 Hannover, Germany
Stephan C. Bischoff
aDepartment of Gastroenterology and Hepatology, Medical School Hannover, D-30625 Hannover, Germany
Abbreviations used in this paper: BrdU, 5-bromo-2′-deoxyuridine; FB, fibroblast; HUVEC, human umbilical vein endothelial cell; ICAM, intracellular adhesion molecule; MC, mast cell; MCT, tryptase-positive MC(s); MCTC, tryptase and chymase double-positive MC(s); mSCF, membrane-bound SCF; SCF, stem cell factor; sSCF, soluble SCF; VCAM, vascular adhesion molecule; VLA-4, very late antigen 4.
Received:
May 08 2000
Revision Requested:
July 18 2000
Accepted:
July 24 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 192 (6): 801–812.
Article history
Received:
May 08 2000
Revision Requested:
July 18 2000
Accepted:
July 24 2000
Citation
Claudia T. Mierke, Matthias Ballmaier, Uwe Werner, Michael P. Manns, Karl Welte, Stephan C. Bischoff; Human Endothelial Cells Regulate Survival and Proliferation of Human Mast Cells. J Exp Med 18 September 2000; 192 (6): 801–812. doi: https://doi.org/10.1084/jem.192.6.801
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