Vascular endothelial growth factor-C promotes alloimmunity by amplifying antigen-presenting cell maturation and lymphangiogenesis

Amir R. Hajrasouliha, Toshinari Funaki, Zahra Sadrai, Takaaki Hattori, Sunil K. Chauhan, Reza Dana

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

PURPOSE. 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.

Original languageEnglish (US)
Pages (from-to)1244-1250
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume53
Issue number3
DOIs
StatePublished - Mar 2012

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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