ANGIOGENIC FACTORS STIMULATE MAST-CELL MIGRATION

Mast cells accumulate at sites of angiogenesis. The factor(s) that con trol mast-cell recruitment at these sites have yet to be defined. We s ought to determine if angiogenic factors result in mast-cell chemotaxi s. In this study, we observed that platelet-derived growth factor-AB ( PDGF-AB), vascular endothelial cell growth factor (VEGF), and basic fi broblast growth factor (bFGF) each cause directed migration of murine mast cells at picomolar concentrations, with a typical bell-shaped dos e-response curve. Another potent angiogenic factor, platelet-derived e ndothelial cell growth factor (PD-ECGF), appears to promote chemokines is of mast cells, whereas tumor necrosis factor-alpha, a weak angiogen ic factor, is less robust but still functions as a mast cell chemotact ic factor. Epidermal growth factor (EGF), a growth factor with minimal angiogenic properties, was ineffective as a mast cell chemotactic fac tor. A checkerboard analysis confirmed the directional chemotactic res ponse of PDGF-AB, VEGF, and bFGF, while indicating the chemokinetic re sponse induced by PD-ECGF. Cross-desensitization of growth-factor-indu ced directed migration was observed between PDGF-AB and bFGF, and also between PDGF-AB and PD-ECGF. Tyrosine kinase-inhibitor genistein effe ctively dampened the chemotactic responses, whereas pertussis toxin ha d no effect. In summary, our findings suggest that factors known to ac t on endothelial cells and stimulate neovascularization may simultaneo usly serve to recruit mast cells to these sites. The local accumulatio n of mast cells is believed to facilitate new vessel formation through complex cell:cell interactions. (C) 1995 by The American Society of H ematology.