Very late antigen 1 blockade markedly promotes survival of corneal allografts.
OBJECTIVE
To investigate the role of very late antigen 1 (VLA-1) (also known as integrin receptor alpha(1)beta(1)) in corneal transplantation inflammation and allograft survival.


METHODS
Cell infiltration and vasculogenesis (both angiogenesis and lymphangiogenesis) associated with allodisparate corneal transplantation were assessed in VLA-1-deficient conditions and controls by immunofluorescent microscopic studies. Corneal allograft survival was also assessed after anti-VLA-1 antibody treatment and in VLA-1 knockout recipient mice.


RESULTS
Anti-VLA-1 antibody treatment leads to a profound reduction in the granulocytic, monocytic, and T-cell infiltration after corneal transplantation. In addition, corneal angiogenesis and lymphangiogenesis were both significantly suppressed in VLA-1 knockout mice. Remarkably, universal graft survival was observed in both anti-VLA-1 antibody treatment and knockout mice.


CONCLUSIONS
Very late antigen 1 blockade markedly reduces inflammation and inflammation-induced tissue responses, including vasculogenic responses, associated with corneal transplantation and promotes allograft survival.


CONCLUSIONS
These studies offer insights into important integrin-mediated mechanisms of corneal transplant-related inflammation and provide possible new integrin-based immunotherapies for transplant rejection.
Chen
Lu
L
Laboratory of Immunology, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, 20 Staniford St, Boston, MA, USA.
Huq
Syed
S
Gardner
Humphrey
H
de Fougerolles
Antonin R
AR
Barabino
Stefano
S
Dana
M Reza
MR
D000818:Animals; D003315:Cornea / Q000502:physiology*; D016510:Corneal Neovascularization / Q000517:prevention & control; D016039:Corneal Transplantation; D020868:Gene Silencing; D006023:Glycoproteins / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology*; D039222:Integrin alpha1beta1 / Q000502:physiology*; D042583:Lymphangiogenesis; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D006023:Glycoproteins; D039222:Integrin alpha1beta1; D016177:Macrophage-1 Antigen; D026901:Membrane Transport Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019707:Receptors, Chemokine; C503133:Gr-1 protein, mouse; C492273:LYVE1 protein, mouse