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Mast Cells Can Secrete Vascular Permeability Factor/ Vascular Endothelial Cell Growth Factor and Exhibit Enhanced Release after Immunoglobulin E–dependent Upregulation of Fc Receptor I Expression

From the Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215

Vascular permeability factor/vascular endothelial cell growth factor (VPF/VEGF) can both potently enhance vascular permeability and induce proliferation of vascular endothelial cells. We report here that mouse or human mast cells can produce and secrete VPF/VEGF. Mouse mast cells release VPF/VEGF upon stimulation through Fc receptor I (FcRI) or c-kit, or after challenge with the protein kinase C activator, phorbol myristate acetate, or the calcium ionophore, A23187; such mast cells can rapidly release VPF/VEGF, apparently from a preformed pool, and can then sustain release by secreting newly synthesized protein. Notably, the FcRI-dependent secretion of VPF/VEGF by either mouse or human mast cells can be significantly increased in cells which have undergone upregulation of FcRI surface expression by a 4-d preincubation with immunoglobulin E. These findings establish that at least one cell type, the mast cell, can be stimulated to secrete VPF/VEGF upon immunologically specific activation via a member of the multichain immune recognition receptor family. Our observations also identify a new mechanism by which mast cells can contribute to enhanced vascular permeability and/or angiogenesis, in both allergic diseases and other settings.

Key Words: allergy • angiogenesis • c-kit • stem cell factor • vascular permeability

Abbreviations used: Act D, Actinomycin D; BMCMC, mouse bone marrow–derived cultured mast cell(s); FBS, fetal bovine serum; HSA, human serum albumin; HMC, umbilical cord blood–derived human mast cell(s); 5-HT, 5-hydroxytryptamine; ISH, in situ hybridization; PMC, peritoneal mast cell(s); rhSCF, recombinant-methionyl human stem cell factor; rrSCF, recombinant rat stem cell factor¹⁶⁴; SCF, stem cell factor; VPF/VEGF, vascular permeability factor/vascular endothelial cell growth factor.

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