The role of CC chemokine receptor 2 in alveolar monocyte and neutrophil immigration in intact mice
The role of CC chemokine receptor 2 in alveolar monocyte and neutrophil immigration in intact mice
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DOI：
10.1164/rccm.2112012
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发表时间：
2002-08-01
影响因子：
24.7
通讯作者：
Lohmeyer, J
中科院分区：
文献类型：
--
作者：
Maus, U;von Grote, K;Lohmeyer, J
CC 趋化因子配体 2 (CCL2)（JE，单核细胞趋化蛋白-1 [MCP-1]）及其 CC 趋化因子受体 2 (CCR2) 是单核细胞/巨噬细胞运输的关键调节因子。最近，我们证明，在小鼠肺部应用外源性 CCL2 会诱导单核细胞在空腔中积聚，而 CCL2 和大肠杆菌环毒素联合支气管肺泡滴注会引起单核细胞积聚增加和与肺内皮/上皮屏障功能丧失相关的广泛中性粒细胞流入。在这项研究中，我们研究了 CCL2 受体 CCR2 在肺泡白细胞运输中的作用。在用抗 CCR2 阻断单克隆抗体 MC21 治疗的 CCR2 敲除小鼠或野生型小鼠中，对肺泡 CCL2 或 CCL2 加环毒素反应的单核细胞积聚被抑制了 90% 以上。出乎意料的是，两种 CCR2 功能干扰方法也大大减少了 CCL2/脂多糖 (LPS) 模型中肺泡中性粒细胞的积累。当用抗 Gr-1 单克隆抗体选择性地消耗中性粒细胞或用抗白细胞酸盐（一种 CXC 受体抑制剂）治疗的野生型小鼠接受肺泡 CCL2 加 LPS 攻击时，肺泡单核细胞积累显着减少。用 MC21 治疗以阻断 CCR2 功能或用抗 Gr-1 治疗以消耗中性粒细胞的野生型小鼠没有表现出通常伴随野生型小鼠中 CCL2 和 LIPS 引发的炎症的血管渗漏。这些发现证实了 CCR2 在肺泡单核细胞招募过程中的核心作用，以响应单独的 CCL2 和 CCL2 加 LPS 的组合，并揭示了单核细胞和中性粒细胞运输之间以前未观察到的相互依赖性，这对于血管通透性的伴随增加具有重要意义。
The CC chemokine ligand 2 (CCL2) (JE, monocyte chemotactic protein-1 [MCP-1]) and its CC chemokine receptor 2 (CCR2) are critical regulators of monocyte/macrophage trafficking. Recently, we demonstrated that application of exogenous CCL2 in the lungs of mice induced monocyte accumulation in the airspace, whereas combined bronchoalveolar instillation of CCL2 and Escherichia coli enclotoxin provoked both enhanced monocyte accumulation and extensive neutrophil influx associated with loss of pulmonary endothelial/epithelial barrier function. In this study, we investigated the role of the CCL2 receptor CCR2 in alveolar leukocyte traffic. In CCR2 knockout mice or wild-type mice treated with the anti-CCR2-blocking monoclonal antibody MC21, monocyte accumulation in response to alveolar CCL2 or CCL2 plus enclotoxin was inhibited by more than 90%. Unexpectedly, alveolar neutrophil accumulation in the CCL2/lipopolysaccharide (LPS) model was also drastically reduced by both approaches of CCR2 function interference. When wild-type mice treated with anti-Gr-1 monoclonal antibody to deplete neutrophils selectively or treated with antileukinate, a CXC receptor inhibitor, were challenged with alveolar CCL2 plus LPS, alveolar monocyte accumulation was markedly decreased. Wild-type mice treated with MC21 to block CCR2 function or with anti-Gr-1 to deplete neutrophils did not exhibit the vascular leakage that typically accompanies inflammation triggered by CCL2 and LIPS in wild-type mice. These findings confirm a central role for CCR2 in the process of alveolar monocyte recruitment in response to CCL2 alone and combined CCL2 plus LPS and reveal a previously unobserved interdependence between monocyte and neutrophil trafficking that has important implications for the concomitant increase in vascular permeability.