Expression of vascular endothelial growth factor by human eosinophils: upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5.
Vascular endothelial growth factor (VEGF) is a pleiotropic polypeptide that mediates endothelial-cell-specific responses such as induction of proliferation and vascular leakage. We examined the expression of VEGF messenger RNA (mRNA) and protein by human eosinophils in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5). Immunoreactive VEGF protein was detected in freshly isolated eosinophils by immunocytochemistry. Eosinophils spontaneously released VEGF protein in culture medium, and this release was upregulated by GM-CSF or IL-5. Freshly isolated eosinophils constitutively expressed VEGF mRNA. Although incubation of eosinophils in culture medium reduced steady-state VEGF mRNA levels, eosinophil VEGF mRNA levels were enhanced by GM-CSF and IL-5, and this enhancement was blocked by the transcription inhibitor actinomycin D. Analysis of alternatively spliced mRNA species revealed that eosinophils contained transcripts mainly encoding for the 121- and 165-amino-acid forms of VEGF. VEGF mRNA expression and VEGF release in cytokine-stimulated eosinophils were significantly reduced by treatment with a glucocorticosteroid, a protein-tyrosine kinase inhibitor, or a protein kinase C inhibitor. Cytokine-activated eosinophils may be an important source of a vascular permeability factor, namely VEGF, thus contributing to tissue edema formation at sites of allergic inflammation.
Horiuchi
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Department of Medicine, Harvard Thorndike Laboratories, Boston, Massachusetts, USA.
Weller
P F
PF
D000470:Alkaloids; D017398:Alternative Splicing; D053119:Benzophenanthridines; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014644:Genetic Variation; D019833:Genistein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D008222:Lymphokines / Q000096:biosynthesis* / Q000097:blood; D010617:Phenanthridines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000470:Alkaloids; D053119:Benzophenanthridines; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D015848:Interleukin-5; D007529:Isoflavones; D008222:Lymphokines; D010617:Phenanthridines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019833:Genistein; C016299:chelerythrine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C