Effect of macrophage depletion by liposomes containing dichloromethylene-diphosphonate on endotoxin-induced uveitis
Effect of macrophage depletion by liposomes containing dichloromethylene-diphosphonate on endotoxin-induced uveitis
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DOI：
10.1016/s0165-5728(98)00042-3
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发表时间：
1998-06-15
影响因子：
3.3
通讯作者：
de Kozak, Y
中科院分区：
文献类型：
--
作者：
Pouvreau, I;Zech, JC;de Kozak, Y
在刘易斯大鼠足垫注射来自鼠伤寒沙门氏菌的脂多糖（LPS）诱导急性前部和后部内毒素诱导的葡萄膜炎（EIU）。为了研究巨噬细胞在EIU发病机制中的作用，我们通过含有二氯亚甲基二膦酸盐（Cl 2 MDP）的脂质体消除了巨噬细胞，Cl 2 MDP是一种消耗巨噬细胞但不消耗其他免疫活性细胞的药物。静脉注射CL 2 MDP-脂质体明显抑制眼前段（虹膜/睫状体）葡萄膜炎的临床和组织学表现，并降低房水中的TNF水平。特异性免疫染色显示，CL 2 MDP-脂质体注射减少了虹膜/睫状体和脉络膜中ED 2+驻留巨噬细胞的数量。在LPS注射后，CL 2 MDP-脂质体处理降低了虹膜/睫状体中而不是脉络膜中的浸润性ED 1+细胞（主要是单核细胞/巨噬细胞）的密度;检测到对0X 42+细胞浸润（主要是多形核白细胞）几乎没有影响。视网膜的炎性细胞浸润没有被治疗改变。这些发现表明，巨噬细胞在眼部炎症的发病机制中起关键作用。(C)1998 Elsevier Science B. V.保留所有权利。
Footpad injection of lipopolysaccharide (LPS) from Salmonella typhimurium in Lewis rats induces an acute anterior and posterior endotoxin-induced uveitis (EIU). To investigate the role of macrophages in the pathogenesis of EIU, we eliminated macrophages by means of liposomes containing dichloromethylene-diphosphonate (Cl2MDP), a drug which depletes macrophages but not other immunocompetent cells. Intravenous injection of CL2MDP-liposomes clearly inhibited clinical and histological manifestations of uveitis in the anterior segment of the eye (iris/ciliary body) and reduced TNF level in aqueous humor. Specific immunostaining showed that CL2MDP-liposome injections decreased the number of ED2 + resident macrophages in the iris/ciliary body and the choroid. After LPS injection, CL2MDP-liposome treatment reduced the density of infiltrating ED1 + cells (mainly monocytes / macrophages) in the iris/ciliary body but not in the choroid; little or no effect was detected on the OX42 + cellular infiltration (mainly polymorphonuclear leukocytes). The inflammatory cellular infiltration of the retina was not modified by the treatment. These findings suggest that macrophages play a key role in the pathogenesis of ocular inflammation. (C) 1998 Elsevier Science B.V. All rights reserved.