Monocyte chemoattractant protein 1 contributes to an adequate immune response in influenza pneumonia

Monocyte chemoattractant protein 1 contributes to an adequate immune response in influenza pneumonia
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DOI:
10.1016/j.clim.2007.08.001
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发表时间:
2007-12-01
影响因子:
8.6
通讯作者:
van der Poll, Tom
van der Poll, Tom
中科院分区:
医学3区
文献类型:
--
作者:
Dessing, Mark C.;van der Sluijs, Koenraad F.;van der Poll, Tom

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单核细胞趋化蛋白1(MCP-1)及其受体CCR2在感染和炎症部位的白细胞募集中起重要作用。为了探讨MCP-1在流感感染中的作用,我们用非致死量的甲型流感病毒感染野生型(WT)和MCP-1基因敲除(KO)小鼠,发现WT小鼠感染流感后肺组织MCP-1水平显著升高。在14天的观察期内,MCP-1 KO小鼠的甩体能力增强,体重没有完全恢复。此外,MCP-1 KO小鼠在感染后8天表现出病毒载量增加,伴随着白细胞向感染肺的募集减少,主要是由于巨噬细胞和粒细胞流入减少所致。此外,MCP-1 KO小鼠肺组织中的IgA水平也降低。MCP-1KO小鼠肺组织中肿瘤坏死因子-α、白介素6、巨噬细胞炎性蛋白-2和干扰素-γ浓度较高。这项研究表明,MCP-1对小鼠的流感感染具有足够的保护性免疫反应。(C)2007 Elsevier Inc.保留所有权利。
Monocyte chemoattractant protein 1 (MCP-1) and its receptor CCR2 have been shown to play an import role in leukocyte recruitment to sites of infection and inflammation. To investigate the role of MCP-1 during infection with influenza we inoculated wild-type (WT) and MCP-1 knockout (KO) mice with a non-lethal dose of a mouse adapted strain of influenza A. Influenza infection of WT mice resulted in a profound increase in pulmonary MCP-1 levels. MCP-1 KO mice had enhanced weight toss and did not fully regain their body weight during the 14-day observation period. In addition, MCP-1 KO mice demonstrated elevated viral loads 8 days after infection, which was accompanied by reduced leukocyte recruitment into the infected lungs, primarily caused by a diminished influx of macrophages and granulocytes. Moreover, pulmonary levels of IgA were reduced in MCP-1 KO mice. The pulmonary concentrations of tumor necrosis factor-alpha, interleukin-6, macrophage inflammatory protein 2 and interferon-gamma were higher in MCP-1 KO mice. This study shows that MCP-1 contributes to an adequate protective immune response against influenza infection in mice. (c) 2007 Elsevier Inc. All rights reserved.