In vivo properties of monocyte chemoattractant protein-1
In vivo properties of monocyte chemoattractant protein-1
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DOI：
10.1002/jlb.62.5.577
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发表时间：
1997-11-01
影响因子：
5.5
通讯作者：
Rollins, B
中科院分区：
文献类型：
--
作者：
Gu, L;Rutledge, B;Rollins, B
单核细胞趋化蛋白-1（MCP-1）在体外吸引单核细胞、记忆T淋巴细胞和自然杀伤（NK）细胞，其表达已被记录在以单核细胞浸润为特征的疾病中，表明其可能有助于动脉粥样硬化、多发性硬化或类风湿性关节炎等疾病的炎症组分，为了证明因果关系，必须了解MCP-1的体内性质，已经构建了几个转基因小鼠品系来解决这个问题。其中MCP-1表达受MMTV-LTR控制的转基因品系在多个器官中表达高水平的MCP-1，但没有显示单核细胞浸润的证据。相反，这些小鼠对细胞内病原体单核细胞增生李斯特菌和结核分枝杆菌的感染更敏感。这些小鼠具有高的MCP-1血清水平，表明它们的循环单核细胞可能已经脱敏或者MCP-1刺激了Th 2-显性应答。相反，其中MCP-1表达受胰岛素启动子控制的另一个模型证实了胰岛中的单核细胞浸润。这些结果表明，在解剖学限定区域中低水平的MCP-1表达导致单核细胞浸润，这表明当适当表达时，MCP-1的体外特性在体内重现，这证明在疾病模型中检查MCP-1缺陷小鼠以探索MCP-1在发病机制中的作用是合理的。
Monocyte chemoattractant protein-1 (MCP-1) attracts monocytes, memory T lymphocytes, and natural killer (NK) cells in vitro, Its expression has been documented in disorders characterized by mononuclear cell infiltrates, suggesting that it may contribute to the inflammatory component of such diseases as atherosclerosis, multiple sclerosis, or rheumatoid arthritis, To prove a causal association, the in vivo properties of MCP-1 must be understood, Several lines of transgenic mice have been constructed to address this question, A transgenic line in which MCP-1 expression is controlled by the MMTV-LTR expressed high levels of MCP-1 in multiple organs but showed no evidence for monocyte infiltration, Instead, these mice were more susceptible to infection by the intracellular pathogens, Listeria monocytogenes and Mycobacterium tuberculosis, These mice had high serum levels of MCP-1, suggesting that their circulating monocytes may have been desensitized or that MCP-1 stimulated a Th2-dominant response, In contrast, another model in which MCP-1 expression was controlled by the insulin promoter demonstrated a monocytic infiltrate in pancreatic islets, These results indicate that MCP-1 expression at low levels in an anatomically confined area results in monocyte infiltration, suggesting that when properly expressed, MCP-1's in vitro properties are reproduced in vivo, This justifies the examination of MCP-1-deficient mice in disease models in order to explore MCP-1's role in pathogenesis.