MAST-CELLS CAN SECRETE VASCULAR-PERMEABILITY FACTOR VASCULAR ENDOTHELIAL-CELL GROWTH-FACTOR AND EXHIBIT ENHANCED RELEASE AFTER IMMUNOGLOBULIN E-DEPENDENT UP-REGULATION OF FC-EPSILON RECEPTOR-I EXPRESSION

Vascular permeability factor/vascular endothelial cell growth factor ( VPF/VEGF) can both potently enhance vascular permeability and induce p roliferation 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 epsilon receptor I (Fc e psilon RI) or c-kit, or after challenge with the protein kinase C acti vator, phorbol myristate acetate, or the calcium ionophore, A23187; su ch mast cells can rapidly release VPF/VEGF, apparently from a preforme d pool, and can then sustain release by secreting newly synthesized pr otein. Notably, the Fc epsilon RI-dependent secretion of VPF/VEGF by e ither mouse or human mast cells can be significantly increased in cell s which have undergone upregulation of Fc epsilon RI surface expressio n by a 4-d preincubation with immunoglobulin E. These finding; establi sh that at least one cell type, the mast cell, can be stimulated to se crete VPF/VEGF upon immunologically specific activation via a member o f the multichain immune recognition receptor family. Our observations also identify a new mechanism by which mast cells can contribute to en hanced vascular permeability and/or angiogenesis, in both allergic dis eases and other settings.