title: Vascular endothelial growth factor-C promotes alloimmunity by amplifying antigen-presenting cell maturation and lymphangiogenesis.
abstract: OBJECTIVE
  To investigate the role of anti-vascular endothelial growth factor (VEGF)-C therapy in corneal graft survival and concomitant suppression of hem- and lymph-angiogenesis.
  
  
  METHODS
  Corneal suture model in BALB/c mice was placed and immunohistochemical staining was performed with CD31/PECAM-1 and LYVE-1 to quantify the level of blood and lymphatic vessels. Corneal transplants were done in BALB/c mice from C57BL/6 mice donors; grafts were subsequently scored for opacity. VEGF-C was blocked in the angiogenesis and transplant model using neutralizing monoclonal anti-VEGF-C (VGX-100) by intraperitoneal injection. To determine the function of VEGF-C in maturation of antigen-presenting cells (APCs), bone marrow-derived dendritic cells were generated and matured in the presence or absence of VEGF-C.
  
  
  RESULTS
  VEGF-C expression was demonstrated to be markedly upregulated in corneal graft rejection. VEGF-C blockade, through administration of a VEGF-C blocking monoclonal antibody, suppresses corneal angiogenic responses, inhibits trafficking and maturation of APCs, and significantly improves allotransplant survival.
  
  
  CONCLUSIONS
  These data suggest VEGF-C as a potentially important target in corneal transplant pharmacotherapy and immunobiology.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Amir R
authors.initials: AR
authors.lastname: Hajrasouliha
authors.forename: Toshinari
authors.initials: T
authors.lastname: Funaki
authors.forename: Zahra
authors.initials: Z
authors.lastname: Sadrai
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hattori
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D015551:Autoimmunity / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D016039:Corneal Transplantation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D007150:Immunohistochemistry; D042583:Lymphangiogenesis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous; D042582:Vascular Endothelial Growth Factor C / Q000494:pharmacology*
chemical_list: D042582:Vascular Endothelial Growth Factor C