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PMID: 9169499 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor.

The Journal of clinical investigation ·Vol. 99 ·No. 11 ·1997-06-01 ·Pages 2691-700

Blair RJ, Meng H, Marchese MJ, Ren S, Schwartz LB, Tonnesen MG, Gruber BL

Abstract

The presence of mast cells near capillary sprouting sites suggests an association between mast cells and angiogenesis. However, the role of mast cells in blood vessel development remains to be defined. In an attempt to elucidate this relationship, we investigated the effect of human mast cells (HMC-1) and their products on human dermal microvascular endothelial cell (HDMEC) tube formation. Coculture of HMC-1 with HDMEC led to a dose-response increase in the network area of vascular tube growth. Moreover, the extent of neovascularization was enhanced greatly when HMC-1 were degranulated in the presence of HDMEC. Further examination using antagonists to various mast cell products revealed a blunted response (73-88% decrease) in the area of vascular tube formation if specific inhibitors of tryptase were present. Tryptase (3 microg/ml) directly added to HDMEC caused a significant augmentation of capillary growth, which was suppressed by specific tryptase inhibitors. Tryptase also directly induced cell proliferation of HDMEC in a dose-dependent fashion (2 pM-2 nM). Our results suggest that mast cells act at sites of new vessel formation by secreting tryptase, which then functions as a potent and previously unrecognized angiogenic factor.

MeSH Terms
Angiogenesis Inducing Agents/pharmacology,physiology Cell Communication Chymases Endothelium, Vascular/cytology Humans Mast Cells/cytology,physiology Neovascularization, Physiologic/drug effects Serine Endopeptidases/pharmacology,physiology Tryptases
Chemicals
Angiogenesis Inducing Agents Serine Endopeptidases chymase 2 Chymases Tryptases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Blair R J
Department of Medicine, SUNY at Stony Brook and Department of Veterans Affairs Medical Center, Northport, New York 11768, USA.
Meng H
Marchese M J
Ren S
Schwartz L B
Tonnesen M G
Gruber B L
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119458
Published
1997-06-01
Pages
2691-700
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508115
Subset
IM
Grants
NIAID NIH HHS · AI20487 · United States
NIAID NIH HHS · AI27517 · United States
External Links
PubMed source DOI: 10.1172/JCI119458 PMC Full Text View journal details
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