Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2
Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2
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DOI：
10.1073/pnas.94.22.12053
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发表时间：
1997-10-28
影响因子：
11.1
通讯作者：
Maeda, N
中科院分区：
文献类型：
--
作者：
Kuziel, WA;Morgan, SJ;Maeda, N
CC趋化因子受体2（CCR 2）是CC趋化因子的单核细胞趋化蛋白（MCP）组的主要受体。通过基因靶向以缺乏CCR 2产生的小鼠表现出正常的白细胞滚动，但在MCP-1诱导的白细胞牢固粘附于微血管内皮和减少的白细胞外渗方面具有明显缺陷。组成性巨噬细胞运输到腹膜腔中在CCR 2缺陷型小鼠和野生型小鼠之间没有显著差异。然而，在腹膜内巯基乙酸盐注射后，CCR 2缺陷型小鼠中的腹腔巨噬细胞的数量没有上升到高于基础水平，而在野生型小鼠中，36小时时的巨噬细胞的数量大约是基础水平的3.5倍，CCR 2缺陷小鼠表现出中性粒细胞和嗜酸性粒细胞的早期蓄积增强和清除延迟。然而，到第5天，CCR 2缺陷型小鼠和野生型小鼠中的中性粒细胞和嗜酸性粒细胞均恢复到接近基础水平，表明在没有巨噬细胞流入和CCR 2介导的常驻腹膜巨噬细胞活化的情况下，这种炎症反应可以消退。静脉注射酵母β-葡聚糖后，野生型小鼠在整个肝实质中形成许多大的、边界清楚的肉芽肿，而CCR 2缺陷小鼠的肉芽肿要少得多且更小，这些结果表明CCR 2是体内诱导巨噬细胞运输的主要调节因子。
CC chemokine receptor 2 (CCR2) is a prominent receptor for the monocyte chemoattractant protein (MCP) group of CC chemokines. Mice generated by gene targeting to lack CCR2 exhibit normal leukocyte rolling but have a pronounced defect in MCP-l-induced leukocyte firm adhesion to microvascular endothelium and reduced leukocyte extravasation, Constitutive macrophage trafficking into the peritoneal cavity was not significantly different between CCR2-deficient and wild-type mice, However, after intraperitoneal thioglycollate injection, the number of peritoneal macrophages in CCR2-deficient mice did not rise above basal levels, whereas in wild-type mice the number of macrophages at 36 h was approximate to 3.5 times the basal level, The CCR2-deficient mice showed enhanced early accumulation and delayed clearance of neutrophils and eosinophils. However, by 5 days neutrophils and eosinophils in both CCR2-deficient and wildtype mice had returned to near basal levels, indicating that resolution of this inflammatory response can occur in the absence of macrophage influx and CCR2-mediated activation of the resident peritoneal macrophages, After intravenous injection with yeast beta-glucan, wild-type mice formed numerous large, well-defined granulomas throughout the liver parenchyma, whereas CCR2-deficient mice had much fewer and smaller granulomas, These results demonstrate that CCR2 is a major regulator of induced macrophage trafficking in vivo.