极晚期抗原1阻断显著促进同种异体角膜移植的存活。
Very late antigen 1 blockade markedly promotes survival of corneal allografts.
作者信息
Chen Lu, Huq Syed, Gardner Humphrey, de Fougerolles Antonin R, Barabino Stefano, Dana M Reza
机构信息
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.
出版信息
Arch Ophthalmol. 2007 Jun;125(6):783-8. doi: 10.1001/archopht.125.6.783.
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.
目的
研究极迟抗原1（VLA-1，也称为整合素受体α(1)β(1)）在角膜移植炎症和同种异体移植存活中的作用。
方法
通过免疫荧光显微镜研究，在VLA-1缺陷条件下和对照中评估与异种角膜移植相关的细胞浸润和血管生成（包括血管生成和淋巴管生成）。在抗VLA-1抗体治疗后以及在VLA-1基因敲除受体小鼠中也评估了角膜同种异体移植的存活情况。
结果
抗VLA-1抗体治疗导致角膜移植后粒细胞、单核细胞和T细胞浸润显著减少。此外，VLA-1基因敲除小鼠的角膜血管生成和淋巴管生成均受到显著抑制。值得注意的是，在抗VLA-1抗体治疗组和基因敲除小鼠中均观察到移植普遍存活。
结论
极迟抗原1阻断可显著减轻与角膜移植相关的炎症以及炎症诱导的组织反应，包括血管生成反应，并促进同种异体移植存活。
临床意义
这些研究为整合素介导的角膜移植相关炎症的重要机制提供了见解，并为移植排斥反应提供了基于整合素的新型免疫治疗方法。
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