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Angiogenic factors stimulate mast-cell migration
BL Gruber, MJ Marchese and R Kew
Department of Medicine, SUNY at Stony Brook 11794-8161, USA.
Mast cells accumulate at sites of angiogenesis. The factor(s) that control
mast-cell recruitment at these sites have yet to be defined. We sought to
determine if angiogenic factors result in mast-cell chemotaxis. In this
study, we observed that platelet-derived growth factor-AB (PDGF-AB),
vascular endothelial cell growth factor (VEGF), and basic fibroblast growth
factor (bFGF) each cause directed migration of murine mast cells at
picomolar concentrations, with a typical bell- shaped dose-response curve.
Another potent angiogenic factor, platelet- derived endothelial cell growth
factor (PD-ECGF), appears to promote chemokinesis of mast cells, whereas
tumor necrosis factor-alpha, a weak angiogenic factor, is less robust but
still functions as a mast cell chemotactic factor. Epidermal growth factor
(EGF), a growth factor with minimal angiogenic properties, was ineffective
as a mast cell chemotactic factor. A checkerboard analysis confirmed the
directional chemotactic response of PDGF-AB, VEGF, and bFGF, while
indicating the chemokinetic response induced by PD-ECGF.
Cross-desensitization of growth-factor-induced directed migration was
observed between PDGF-AB and bFGF, and also between PDGF-AB and PD-ECGF.
Tyrosine kinase- inhibitor genistein effectively dampened the chemotactic
responses, whereas pertussis toxin had no effect. In summary, our findings
suggest that factors known to act on endothelial cells and stimulate
neovascularization may simultaneously serve to recruit mast cells to these
sites. The local accumulation of mast cells is believed to facilitate new
vessel formation through complex cell:cell interactions.
Volume 86,
Issue 7,
pp. 2488-2493,
10/01/1995
Copyright © 1995 by The American Society of Hematology
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