A mechanism for the impaired IFN-γ production in C-C chemokine receptor 2 (CCR2) knockout mice:: Role of CCR2 in linking the innate and adaptive immune responses
A mechanism for the impaired IFN-γ production in C-C chemokine receptor 2 (CCR2) knockout mice:: Role of CCR2 in linking the innate and adaptive immune responses
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DOI：
10.4049/jimmunol.165.12.7072
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发表时间：
2000-12-15
影响因子：
4.4
通讯作者：
Charo, IF
中科院分区：
文献类型：
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作者：
Peters, W;Dupuis, M;Charo, IF
我们最近发现，定向阻断CCR2的小鼠，单核细胞趋化蛋白-1的受体，显著地损害了巨噬细胞对炎症部位的募集。CCR2(-/-)小鼠的一个意想不到的发现是，在用牛分枝杆菌纯化蛋白衍生物攻击后，干扰素-γ的产生显著减少。在本研究中，我们对这种细胞因子产生缺陷的机制进行了研究。在体外，CD3/CD28抗体对脾细胞的直接激活未能揭示CCR2(+/+)和CCR2(-/-)小鼠在产生干扰素-γ方面的任何差异。然而，免疫后CCR2(-/-)小鼠引流淋巴结中的抗原特异性产生干扰素-γ的细胞数量减少了70%，这表明存在体内转运缺陷。用荧光标记的CFA直接测量细胞移行的结果显示，CCR2(-/-)小鼠向免疫部位和引流淋巴结迁移的单核/巨噬细胞数量显著减少。这些数据表明CCR2(-/-)小鼠体内APC的运输受损导致了干扰素-γ的产生缺陷，这些数据支持了CCR2阳性的单核/巨噬细胞在连接先天免疫反应和获得性免疫反应中的关键作用的观点。
We have recently shown that mice with a targeted disruption of CCR2, the receptor for monocyte chemoattractant protein-1, have markedly impaired recruitment of macrophages to sites of inflammation. An unexpected finding in the CCR2(-/-) mice was a dramatic decrease in the production of IFN-gamma after challenge with purified protein derivative of Mycobacterium bovis. In this study, we have investigated the mechanism of this cytokine production defect. In vitro, direct activation of splenocytes with CD3/CD28 Abs failed to reveal any differences in IFN-gamma production between CCR2(+/+) and CCR2(-/-) mice. However, after immunization, the number of Ag-specific, IFN-gamma -producing cells in the draining lymph nodes was decreased by 70% in the CCR2(-/-) mice, suggesting an in vivo trafficking defect, Direct measurement of cell trafficking with fluorescently labeled CFA revealed a marked decrease in the number of monocytes/macrophages migrating to the site of immunization and to the draining lymph nodes in the CCR2(-/-)mice. The data suggest that impaired trafficking of APCs in the CCR2(-/-) mice contributes to the defect in IFN-gamma production, These data support the idea that CCR2-positive monocytes/macrophages are critical in linking the innate and adaptive immune responses.