Mast cells can secrete vascular permeability factor/ vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of fc epsilon receptor I expression.
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 Fcepsilon receptor I (FcepsilonRI) 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 epsilonRI-dependent secretion of VPF/VEGF by either mouse or human mast cells can be significantly increased in cells which have undergone upregulation of Fc epsilonRI 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.
Boesiger
J
J
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Tsai
M
M
Maurer
M
M
Yamaguchi
M
M
Brown
L F
LF
Claffey
K P
KP
Dvorak
H F
HF
Galli
S J
SJ
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004140:Dinitrophenols / Q000276:immunology / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006241:Haptens / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology*; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000502:physiology; D012709:Serum Albumin / Q000276:immunology / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000276:immunology; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004140:Dinitrophenols; D016228:Endothelial Growth Factors; D006241:Haptens; D008222:Lymphokines; D012333:RNA, Messenger; D017455:Receptors, IgE; D012709:Serum Albumin; D019089:Stem Cell Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C058064:dinitrophenyl-human serum albumin conjugate; D007073:Immunoglobulin E; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate