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

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.

authors

Hajrasouliha AR,Funaki T,Sadrai Z,Hattori T,Chauhan SK,Dana R

doi

10.1167/iovs.11-8668

subject

Has Abstract

pub_date

2012-03-09 00:00:00

pages

1244-50

issue

3

eissn

0146-0404

issn

1552-5783

pii

iovs.11-8668

journal_volume

53

pub_type

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