Impaired hepatic granuloma formation in mice deficient in C-C chemokine receptor 2
Impaired hepatic granuloma formation in mice deficient in C-C chemokine receptor 2
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DOI：
10.1002/path.1362
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发表时间：
2003-07-01
影响因子：
7.3
通讯作者：
Takeya, M
中科院分区：
文献类型：
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作者：
Jinnouchi, K;Terasaki, Y;Takeya, M
肉芽肿的组织学特征是巨噬细胞结节样聚集，偶见上皮样细胞、多核巨细胞和其他免疫活性细胞。趋化因子被认为在肉芽肿的这些组成细胞的募集中起重要作用。本研究检测了C-C趋化因子受体2（CCR 2）缺陷对单次注射酵母多糖A诱导的肝肉芽肿形成的影响。在CCR 2 +/+小鼠中，肉芽肿的数量和大小逐渐增加，直到注射后10天达到峰值。相反，从第5天到第21天，CCR 2-/-小鼠的肉芽肿数量和大小均小于CCR 2 +/+小鼠。第5天出现低峰，此后肉芽肿的数量和大小逐渐减少。使用细胞类型特异性单克隆抗体对组成性肉芽肿细胞进行的免疫组织化学分析显示，在第2-10天期间，CCR 2 +/+小鼠中血液单核细胞快速积聚，随后分化为巨噬细胞。这一过程在CCR 2-/-小鼠中大大受损，肉芽肿仍然很小。在所有时间点，CCR 2-/-小鼠中肉芽肿中的多形核细胞百分比均高于CCR 2 +/+小鼠。有趣的是，在CCR 2-/-小鼠的肉芽肿中经常观察到多核巨细胞，而它们很少出现在CCR 2 +/+小鼠中。肝脏细胞因子RNA水平以及血清细胞因子水平的概况揭示了CCR 2-/-小鼠中Th 1细胞因子IFN-γ的表达减少。这些数据清楚地表明，通过CCR 2的信号传导对肝肉芽肿的正常生长和发育有许多影响。版权所有（C）2003约翰威利父子有限公司。
Granulomas are characterized histologically by a nodular collection of macrophages with occasional admixture of epithelioid cells, multinucleate giant cells, and other immunocompetent cells. Chemokines are considered to play an important role in the recruitment of these constituent cells of granulomas. The present study has examined the effect of a deficiency of C-C chemokine receptor-2 (CCR2) on hepatic granuloma formation induced by a single injection of Zymosan A. In CCR2+/+ mice, the number and the size of granulomas gradually increased until they reached peak values at 10 days after the injection. In contrast, both the number and the size of granulomas were smaller in CCR2-/- mice than in CCR2+/+ mice from days 5 to 21. They showed low peaks at day 5, after which the number and the size of the granulomas gradually decreased. Inummohistochemical analysis of the constituent granuloma cells using cell type-specific monoclonal antibodies revealed rapid accumulation of blood monocytes, with subsequent differentiation to macrophages, in CCR2+/+ mice during days 2-10. This process was greatly impaired in CCR2-/- mice and granulomas remained small. At all time points, the percentage of polymorphonuclear cells in granulomas was higher in CCR2-/- mice than in CCR2+/+ mice. Interestingly, multinucleate giant cells were frequently observed in granulomas in CCR2-/- mice, whereas they rarely appeared in CCR2+/+ mice. Profiles of liver cytokine RNA levels as well as serum cytokine levels revealed reduced expression of the Th1 cytokine IFN-gamma in CCR2-/- mice. These data clearly indicate that signalling through CCR2 has many effects on the normal growth and development of hepatic granulomas. Copyright (C) 2003 John Wiley Sons, Ltd.