Human endothelial cells regulate survival and proliferation of human mast cells.
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 (MC(TC)). 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 MC(TC) development.
Mierke
C T
CT
Department of Gastroenterology and Hepatology, Medical School Hannover, D-30625 Hannover, Germany.
Ballmaier
M
M
Werner
U
U
Manns
M P
MP
Welte
K
K
Bischoff
S C
SC
D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000032:analysis; D007413:Intestinal Mucosa / Q000166:cytology; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000032:analysis / Q000502:physiology; D013997:Time Factors; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology
D000906:Antibodies; D015703:Antigens, CD; D016207:Cytokines; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D019089:Stem Cell Factor; D019010:Vascular Cell Adhesion Molecule-1; D019009:Proto-Oncogene Proteins c-kit