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J. Exp. Med.,
Volume 188, Number 6, September 21, 1998 1135-1145
Receptor I Expression
By
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 (Fc
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
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
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.
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