Tuaillon Nadine, Shen De Fen, Berger Ravi B, Lu Bao, Rollins Barrett J, Chan Chi-Chao
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bldg. 10 Room 10-N-103, 10 Center Drive, Bethesda, MD 20892-1857, USA.
Invest Ophthalmol Vis Sci. 2002 May;43(5):1493-8.
Monocyte chemoattractant protein (MCP)-1 (CCL-2) is a chemokine with chemoattractant properties for monocytes, memory T cells, natural killer cells, mast cells, and basophils. To delineate the role played by MCP-1 in acute anterior uveitis, a common ocular inflammation, MCP-1(-/-) mice and wild-type matched control mice were analyzed for the development of endotoxin-induced uveitis (EIU) in response to subcutaneous injection of a sublethal dose of lipopolysaccharide (LPS).
EIU was induced in MCP-1(-/-) and wild-type control mice by a single subcutaneous injection of Salmonella typhimurium LPS endotoxin at day 0. Alternatively, MCP-1(-/-) mice were injected subcutaneously with LPS plus recombinant MCP-1 at day 0 and with recombinant MCP-1 6 hours later. Mice were killed at day 1 or 3 after injection. Serum levels of IL-1alpha, IL-1beta, IL-6, IFN-gamma, TNF-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein (MIP)-1alpha, MIP-2, regulated on activation normal T-cell expressed and secreted (RANTES), and MCP-1 were determined by ELISA. Eyes were collected and analyzed histologically and by RT-PCR for MCP-1, IFN-gamma, IL-6, TNF-alpha, beta-actin, MCP-5, RANTES, KC, inflammatory protein (IP)-10, and toll-like receptor (TLR)-4.
EIU was strongly reduced in MCP-1(-/-) mice compared with wild-type control mice. The number of ocular inflammatory cells was significantly reduced. Moreover, intraocular IFN-gamma transcription was increased. EIU was induced in MCP-1(-/-) mice by co-administration of recombinant rat MCP-1 and LPS.
Data indicate that MCP-1 plays a crucial role in the induction of EIU. MCP-1 may be a new therapeutic strategy for acute anterior uveitis.
单核细胞趋化蛋白（MCP）-1（CCL-2）是一种对单核细胞、记忆性T细胞、自然杀伤细胞、肥大细胞和嗜碱性粒细胞具有趋化特性的趋化因子。为了阐明MCP-1在急性前葡萄膜炎（一种常见的眼部炎症）中所起的作用，我们分析了MCP-1基因敲除（-/-）小鼠和野生型对照小鼠在皮下注射亚致死剂量脂多糖（LPS）后内毒素诱导性葡萄膜炎（EIU）的发展情况。
在第0天通过单次皮下注射鼠伤寒沙门氏菌LPS内毒素在MCP-1（-/-）和野生型对照小鼠中诱导EIU。或者，在第0天给MCP-1（-/-）小鼠皮下注射LPS加重组MCP-1，并在6小时后注射重组MCP-1。在注射后第1天或第3天处死小鼠。通过酶联免疫吸附测定法（ELISA）测定血清中白细胞介素（IL）-1α、IL-1β、IL-6、干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、巨噬细胞炎性蛋白（MIP）-1α、MIP-2、正常T细胞激活后表达和分泌的调节因子（RANTES）以及MCP-1的水平。收集眼睛并进行组织学分析，通过逆转录-聚合酶链反应（RT-PCR）检测MCP-1、IFN-γ、IL-6、TNF-α、β-肌动蛋白、MCP-5、RANTES、角质形成细胞趋化因子（KC）、炎性蛋白（IP）-10和Toll样受体（TLR）-4。
与野生型对照小鼠相比，MCP-1（-/-）小鼠的EIU明显减轻。眼部炎性细胞数量显著减少。此外，眼内IFN-γ转录增加。通过联合给予重组大鼠MCP-1和LPS在MCP-1（-/-）小鼠中诱导出了EIU。
数据表明MCP-1在EIU的诱导中起关键作用。MCP-1可能是急性前葡萄膜炎的一种新的治疗策略。
