High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens.
High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens.
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DOI：
10.4049/jimmunol.155.10.4838
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发表时间：
1995-11
影响因子：
4.4
通讯作者：
B. Rutledge;H. Rayburn;R. Rosenberg;R. North;R. Gladue;C. Corless;B. Rollins
中科院分区：
文献类型：
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作者：
B. Rutledge;H. Rayburn;R. Rosenberg;R. North;R. Gladue;C. Corless;B. Rollins
我们构建了小鼠乳腺肿瘤病毒长末端重复序列控制鼠单核细胞趋化蛋白-1（MCP-1）表达的转基因小鼠。几个独立衍生系的转基因小鼠组成型表达MCP-1蛋白在各种器官。从这些器官中提取的蛋白质具有大量的体外单核细胞趋化活性，其被抗MCP-1抗体中和，表明转基因MCP-1蛋白具有生物活性。然而，没有转基因小鼠在任何年龄显示单核细胞浸润的MCP-1表达的器官。两个转基因系的循环MCP-1水平为13至26 ng/ml，这是足以在体外诱导最大单核细胞趋化性的浓度。这些转基因株系对单核细胞增生李斯特菌和结核分枝杆菌感染的敏感性增加1至1.5个对数。第三个转基因株系具有较低的MCP-1血清水平，并且对L.单核细胞增多症结果表明，这种转基因模型是一个单核细胞无反应性本地产生的MCP-1由于受体脱敏或中和的化学引诱梯度高全身浓度的MCP-1。无论机制如何，数据表明组成性高水平的MCP-1表达不诱导单核细胞浸润，并且MCP-1参与宿主对细胞内病原体的应答。
We have constructed transgenic mice in which the mouse mammary tumor virus long terminal repeat controls the expression of murine monocyte chemoattractant protein-1 (MCP-1). Several independently derived lines of transgenic mice constitutively expressed MCP-1 protein in a variety of organs. Protein extracts from these organs had substantial in vitro monocyte chemoattractant activity that was neutralized by an anti-MCP-1 Ab, indicating that transgenic MCP-1 protein is biologically active. However, no transgenic mouse at any age displayed monocyte infiltrates in MCP-1-expressing organs. Two transgenic lines had circulating MCP-1 levels of 13 to 26 ng/ml, which is a concentration sufficient to induce maximal monocyte chemotaxis in vitro. These transgenic lines showed a 1 to 1.5 log greater sensitivity to infection with Listeria monocytogenes and Mycobacterium tuberculosis. A third transgenic line had lower serum levels of MCP-1 and was resistant to L. monocytogenes. The results suggest that this transgenic model is one of monocyte nonresponsiveness to locally produced MCP-1 due to either receptor desensitization or neutralization of a chemoattractant gradient by high systemic concentrations of MCP-1. Regardless of the mechanism, the data indicate that constitutively high levels of MCP-1 expression do not induce monocytic infiltrates, and that MCP-1 is involved in the host response to intracellular pathogens.