Abstract
In this study, we find that CD45RO+ memory populations of CD4+ T lymphocytes express the vascular endothelial growth factor (VEGF) receptors KDR and Flt-1 at both the mRNA and protein levels. Furthermore, by Western blot analysis, we find that VEGF increases the phosphorylation and activation of ERK and Akt within CD4+CD45RO+ T cells. These VEGF-mediated signaling responses were inhibited by a KDR-specific small interfering RNA in a VEGF receptor-expressing Jurkat T cell line and by SU5416, a pharmacological KDR inhibitor, in CD4+CD45RO+ T cells. We also find that VEGF augments mitogen-induced production of IFN-gamma in a dose-dependent manner (p < 0.001) and significantly (p < 0.05) increases directed chemotaxis of this T cell subset. Collectively, our results for the first time define a novel function for VEGF and KDR in CD45RO+ memory T cell responses that are likely of great pathophysiological importance in immunity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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CD4-Positive T-Lymphocytes / immunology*
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Cells, Cultured
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Chemotaxis
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Humans
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Immunologic Memory*
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Interferon-gamma / biosynthesis*
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Jurkat Cells
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Leukocyte Common Antigens
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Mitogen-Activated Protein Kinase Kinases / metabolism*
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Proto-Oncogene Proteins c-akt / metabolism*
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RNA, Messenger / analysis
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Signal Transduction / immunology
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Vascular Endothelial Growth Factor A / metabolism*
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Vascular Endothelial Growth Factor Receptor-1 / analysis
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Vascular Endothelial Growth Factor Receptor-1 / genetics
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Vascular Endothelial Growth Factor Receptor-2 / analysis*
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Vascular Endothelial Growth Factor Receptor-2 / genetics
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Vascular Endothelial Growth Factor Receptor-2 / physiology
Substances
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RNA, Messenger
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Vascular Endothelial Growth Factor A
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Interferon-gamma
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FLT1 protein, human
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinase Kinases
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Leukocyte Common Antigens