title: Very late antigen 1 blockade markedly promotes survival of corneal allografts.
abstract: 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.
authors.affiliation: 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.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Syed
authors.initials: S
authors.lastname: Huq
authors.forename: Humphrey
authors.initials: H
authors.lastname: Gardner
authors.forename: Antonin R
authors.initials: AR
authors.lastname: de Fougerolles
authors.forename: Stefano
authors.initials: S
authors.lastname: Barabino
authors.forename: M Reza
authors.initials: MR
authors.lastname: Dana
mesh_terms: 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
chemical_list: 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