The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/9/1135/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 6, September 21, 1998 1135-1145

Articles

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

Jürg Boesiger, Mindy Tsai, Marcus Maurer, Masao Yamaguchi, Lawrence F. Brown, Kevin P. Claffey, Harold F. Dvorak, and Stephen J. Galli

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{varepsilon} receptor I (Fc{varepsilon}RI) 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 Fc{varepsilon}RI-dependent secretion of VPF/VEGF by either mouse or human mast cells can be significantly increased in cells which have undergone upregulation of Fc{varepsilon}RI 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

Address correspondence to Stephen J. Galli, Department of Pathology, RN-227, Beth Israel Deaconess Medical Center-East, P.O. Box 15707, Boston, MA 02215. Phone: 617-667-5970; Fax: 617-667-3616; E-mail: sgalli{at}bidmc.harvard.edu

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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