Archives of ophthalmology (Chicago, Ill. : 1960) · 2007
Very late antigen 1 blockade markedly promotes survival of corneal allografts.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Chen Lu, Huq Syed, Gardner Humphrey, de Fougerolles Antonin R, Barabino Stefano, Dana M Reza
Аннотация
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.
CLINICAL RELEVANCE: These studies offer insights into important integrin-mediated mechanisms of corneal transplant-related inflammation and provide possible new integrin-based immunotherapies for transplant rejection.
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.
CLINICAL RELEVANCE: These studies offer insights into important integrin-mediated mechanisms of corneal transplant-related inflammation and provide possible new integrin-based immunotherapies for transplant rejection.
Предметные рубрики MeSH
AnimalsCorneaCorneal NeovascularizationCorneal TransplantationGene SilencingGlycoproteinsGraft SurvivalIntegrin alpha1beta1LymphangiogenesisMacrophage-1 AntigenMaleMembrane Transport ProteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMicroscopy, FluorescencePlatelet Endothelial Cell Adhesion Molecule-1Receptors, ChemokineT-LymphocytesTransplantation, Homologous