title: Expression of soluble vascular endothelial growth factor receptor-1 in human monocyte-derived mature dendritic cells contributes to their antiangiogenic property.
abstract: The soluble form of vascular endothelial growth factor receptor-1 (sVEGFR-1) is produced from endothelial cells by alternative splicing of VEGFR-1 mRNA, and can inhibit angiogenesis by blocking the biological effects of VEGF. In this study, we show the expression of a large amount of sVEGFR-1 in human monocyte-derived mature dendritic cells (mDCs). As compared with monocytes and immature DCs, mDCs generated by TNF-alpha or soluble CD40L with IFN-gamma, but not LPS or other stimuli, preferentially produce sVEGFR-1. We also detected the mRNA of sVEGFR-1 generated by alternative splicing of VEGFR-1 mRNA in mDCs induced by TNF-alpha. The production of sVEGFR-1 showed a distinct contrast to those of VEGF in each DC matured with various stimuli. The supernatant of DCs matured with TNF-alpha or soluble CD40L with IFN-gamma showed inhibition of the tube formation of HUVECs, which was neutralized by anti-VEGFR-1 Ab, indicating that sVEGFR-1 secreted from mDCs was biologically active. Interestingly, the supernatant of mDCs generated with LPS increased HUVEC capillary-like formation in vitro. The ratio of sVEGFR-1 to VEGF clearly reflected the net angiogenic property of mDCs. Administration of mDCs induced by TNF-alpha into the s.c. tumor of PC-14 cells implanted in SCID mice demonstrated the inhibition of tumor growth via reduction of the number of CD31-positive vessels, indicating their in vivo antiangiogenic potential. These results suggest that sVEGFR-1 produced by mDCs contribute to their antiangiogenic property, and the ratio of sVEGFR-1 to VEGF might be a useful tool for evaluating their ability to regulate angiogenesis mediated by VEGF.
authors.affiliation: Department of Respiratory Medicine and Rheumatology, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kishuku
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nishioka
authors.forename: Shinji
authors.initials: S
authors.lastname: Abe
authors.forename: Jun
authors.initials: J
authors.lastname: Kishi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ogino
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Aono
authors.forename: Momoyo
authors.initials: M
authors.lastname: Azuma
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Rentsenkhand
authors.initials: R
authors.lastname: Batmunkh
authors.forename: Batmungh
authors.initials: B
authors.lastname: Rentsenhand
authors.forename: Hideki
authors.initials: H
authors.lastname: Makino
authors.forename: Priya
authors.initials: P
authors.lastname: Ranjan
authors.forename: Kazuo
authors.initials: K
authors.lastname: Minakuchi
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009368:Neoplasm Transplantation / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1