VEGF164(165) as the pathological isoform: differential leukocyte and endothelial responses through VEGFR1 and VEGFR2
| Autor: | Susumu Ishida, Shiro Amano, Matthew Golding, David T. Shima, Kenji Yamashiro, T Usui, Darlene A. Dartt, Anthony P. Adamis, Yuichi Kaji, V. Poulaki, Johnny Moore, Tara Moore, Yoshitaka Horikawa |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Endothelium Angiogenesis Blotting Western Cell Culture Techniques Vascular permeability Inflammation Biology Corneal inflammation Cornea chemistry.chemical_compound Jurkat Cells Leukocyte Count Mice medicine Animals Humans Protein Isoforms Corneal Neovascularization RNA Messenger Phosphorylation Vascular Endothelial Growth Factor Receptor-1 Reverse Transcriptase Polymerase Chain Reaction Tyrosine phosphorylation Intercellular Adhesion Molecule-1 Vascular Endothelial Growth Factor Receptor-2 Cell biology Vascular endothelial growth factor Mice Inbred C57BL Vascular endothelial growth factor A Chemotaxis Leukocyte medicine.anatomical_structure chemistry Immunology Endothelium Vascular medicine.symptom |
| Zdroj: | Investigative ophthalmologyvisual science. 45(2) |
| ISSN: | 0146-0404 |
| Popis: | Vascular endothelial growth factor (VEGF) induces angiogenesis and vascular permeability and is thought to be operative in several ocular vascular diseases. The VEGF isoforms are highly conserved among species; however, little is known about their differential biological functions in adult tissue. In the current study, the inflammatory potential of two prevalent VEGF isoform splice variants, VEGF(120(121)) and VEGF(164(165)), was studied in the transparent and avascular adult mouse cornea.Controlled-release pellets containing equimolar amounts of VEGF(120) and VEGF(164) were implanted in corneas. The mechanisms underlying this differential response of VEGF isoforms were explored. The response of VEGF in cultured endothelial cells was determined by Western blot analysis. The response of VEGF isoforms in leukocytes was also investigated.VEGF(164) was found to be significantly more potent at inducing inflammation. In vivo blockade of VEGF receptor (VEGFR)-1 significantly suppressed VEGF(164)-induced corneal inflammation. In vitro, VEGF(165) more potently stimulated intracellular adhesion molecule (ICAM)-1 expression on endothelial cells, an effect that was mediated by VEGFR2. VEGF(164) was also more potent at inducing the chemotaxis of monocytes, an effect that was mediated by VEGFR1. In an immortalized human leukocyte cell line, VEGF(165) was found to induce tyrosine phosphorylation of VEGFR1 more efficiently.Taken together, these data identify VEGF(164(165)) as a proinflammatory isoform and identify multiple mechanisms underlying its proinflammatory biology. |
| Databáze: | OpenAIRE |
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