RESUMO
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.
Assuntos
Fatores de Crescimento Endotelial/metabolismo , Imunoglobulina E/fisiologia , Linfocinas/metabolismo , Mastócitos/metabolismo , Receptores de IgE/biossíntese , Regulação para Cima/imunologia , Animais , Calcimicina/farmacologia , Linhagem Celular , Células Cultivadas , Dinitrofenóis/imunologia , Dinitrofenóis/farmacologia , Fatores de Crescimento Endotelial/biossíntese , Fatores de Crescimento Endotelial/genética , Feminino , Haptenos/farmacologia , Humanos , Linfocinas/biossíntese , Linfocinas/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de IgE/fisiologia , Albumina Sérica/imunologia , Albumina Sérica/farmacologia , Fator de Células-Tronco/farmacologia , Acetato de Tetradecanoilforbol/farmacologia , Transcrição Gênica/imunologia , Cordão Umbilical/citologia , Cordão Umbilical/metabolismo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
The cytokine interleukin-3 (IL-3), which can be derived from T cells and other sources, is a potentially important link between the immune and haematopoietic systems. IL-3 may be particularly critical for the development, survival and function of tissue mast cells and blood basophils, which are thought to be important effector cells in immunity to parasites and other immunological responses, such as allergic reactions. Here we show, using IL-3-deficient mice, that IL-3 is not essential for the generation of mast cells or basophils under physiological conditions, but that it does contribute to increased numbers of tissue mast cells, enhanced basophil production, and immunity in mice infected with the nematode Stronglyoides venezuelensis. Parasite expulsion and mast-cell development are impaired even more severely in IL-3-deficient mice that also show a marked reduction in signalling by c-kit. These findings establish a role for IL-3 in immunity to parasites and indicate that one of the functions of IL-3 in host defence against infection is to expand populations of haematopoietic effector cells.