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

33 Citations (Scopus)

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 1 2012
Externally publishedYes

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Lymphangiogenesis
Vascular Endothelial Growth Factor C
Antigen-Presenting Cells
Transplants
CD31 Antigens
Lymphatic Vessels
Blocking Antibodies
Graft Rejection
Lymph
Graft Survival
Intraperitoneal Injections
Inbred C57BL Mouse
Dendritic Cells
Sutures
Blood Vessels
Bone Marrow
Monoclonal Antibodies
Staining and Labeling
Drug Therapy

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Vascular endothelial growth factor-C promotes alloimmunity by amplifying antigen-presenting cell maturation and lymphangiogenesis. / Hajrasouliha, Amir R.; Funaki, Toshinari; Sadrai, Zahra; Hattori, Takaaki; Chauhan, Sunil K.; Dana, Reza.

In: Investigative Ophthalmology and Visual Science, Vol. 53, No. 3, 01.03.2012, p. 1244-1250.

Research output: Contribution to journalArticle

Hajrasouliha, Amir R. ; Funaki, Toshinari ; Sadrai, Zahra ; Hattori, Takaaki ; Chauhan, Sunil K. ; Dana, Reza. / Vascular endothelial growth factor-C promotes alloimmunity by amplifying antigen-presenting cell maturation and lymphangiogenesis. In: Investigative Ophthalmology and Visual Science. 2012 ; Vol. 53, No. 3. pp. 1244-1250.
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AB - 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.

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