在大鼠实验性自身免疫性葡萄膜视网膜炎的效应阶段，骨髓来源的活化巨噬细胞是必需的。

Marrow-derived activated macrophages are required during the effector phase of experimental autoimmune uveoretinitis in rats.

作者信息

Forrester J V, Huitinga I, Lumsden L, Dijkstra C D

机构信息

Department of Ophthalmology, University of Aberdeen, Scotland.

出版信息

Curr Eye Res. 1998 Apr;17(4):426-37. doi: 10.1080/02713689808951224.

DOI:10.1080/02713689808951224

PMID:9561835

Abstract

PURPOSE

Experimental autoimmune uveoretinitis (EAU), an established model for human endogenous (autoimmune) posterior uveitis, is a CD4+ T cell-mediated disease inducible in Lewis rats by intradermal inoculation with retinal antigens. Immunohistochemical studies have previously documented the lymphocyte profiles during various stages of the disease process. The purpose of the present study was to investigate the role of macrophages in EAU.

METHODS

EAU was induced in Lewis rats, and the effect of macrophage depletion, using the drug dichlorodimethylene diphosphonate (Cl2MDP) encapsulated in liposomes and administered intravenously, was assessed based on the clinical and histological profile of the disease.

RESULTS

The results have shown that in control animals macrophages occur early, feature prominently throughout the course of the disease and display considerable heterogeneity: marrow-derived ED1+ cells and ED3+ cells are the major infiltrating cells, with many cells also expressing ED7 and ED8. In contrast, few cells expressed the ED2 antigen during EAU, even though ED2+ "resident" macrophages occur in the normal choroid. Macrophage depletion, using intravenously injected dichloromethylene diphosphonate (Cl2MDP) enclosed in liposomes, caused a delay in the onset and a reduction in the severity of EAU when administered during the "effector" stage of the disease, i.e. 9-11 days after inoculation with retinal antigen. The delay in disease onset was greater when liposomes were mannosylated and was accompanied by a reduction in the overall inflammatory cell infiltrate into the eye and reduced tissue damage. In addition, there was a reduction in the level of expression of MHC Class II antigen and CR3 (ED7) antigen, a marker of macrophage activation, in Cl2MDP-treated animals compared to controls.

CONCLUSION

These results suggest that blood-borne, activated macrophages are major effectors of tissue damage during EAU.

摘要

目的

实验性自身免疫性葡萄膜视网膜炎（EAU）是人类内源性（自身免疫性）后葡萄膜炎的既定模型，是一种通过皮内接种视网膜抗原来诱导Lewis大鼠发病的CD4 + T细胞介导的疾病。免疫组织化学研究先前已记录了疾病过程各个阶段的淋巴细胞谱。本研究的目的是探讨巨噬细胞在EAU中的作用。

方法

在Lewis大鼠中诱导EAU，并基于疾病的临床和组织学特征，评估使用包裹在脂质体中并静脉注射的二氯二甲基二膦酸盐（Cl2MDP）药物清除巨噬细胞的效果。

结果

结果表明，在对照动物中，巨噬细胞早期出现，在疾病过程中始终占显著比例，并表现出相当大的异质性：骨髓来源的ED1 +细胞和ED3 +细胞是主要的浸润细胞，许多细胞还表达ED7和ED8。相比之下，尽管正常脉络膜中存在ED2 +“驻留”巨噬细胞，但在EAU期间很少有细胞表达ED2抗原。在疾病的“效应”阶段，即接种视网膜抗原后9-11天，使用包裹在脂质体中的静脉注射二氯亚甲基二膦酸盐（Cl2MDP）清除巨噬细胞，可导致EAU发病延迟和严重程度降低。当脂质体被甘露糖基化时，疾病发作的延迟更大，同时伴有眼内总体炎性细胞浸润减少和组织损伤减轻。此外，与对照组相比，Cl2MDP处理的动物中MHC II类抗原和CR3（ED7）抗原（巨噬细胞活化的标志物）的表达水平降低。