Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice
Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice
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DOI：
10.1152/ajplung.00453.2001
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发表时间：
2002-06-01
影响因子：
4.9
通讯作者：
Lohmeyer, J
中科院分区：
文献类型：
--
作者：
Maus, UA;Koay, MA;Lohmeyer, J
单核细胞趋化因子JE/单核细胞趋化蛋白-1(JE/MCP-1)在小鼠气管内滴注可在无肺部炎症的情况下引起肺泡单核细胞聚集增加，而JE/MCP-1/脂多糖(LPS)联合刺激可引起早期肺泡中性粒细胞和延迟的肺泡单核细胞内流。我们评估了常驻肺泡巨噬细胞(RAM)在这些白细胞募集事件和相关的肺部炎症现象中的作用。尽管通过流式细胞仪和免疫组织化学分析，观察到Ram结构性地表达JE/MCP-1受体CCR2，但用脂质体克屈酸盐预处理耗尽Ram并不影响JE/MCP-1驱动的肺泡单核细胞聚集。相反，在JE/MCP-1/LPS联合治疗中，Ram的耗竭在很大程度上抑制了肺泡细胞因子的释放以及中性粒细胞和单核细胞的募集。尽管这种强烈减弱的肺泡炎性反应，在接受JE/MCP-1/LPS攻击的Ram耗竭小鼠中仍然观察到肺通透性增加。通过清除循环中的中性粒细胞或给予抗CD18抗体来消除肺渗漏。总的来说，Ram不参与JE/MCP-1驱动的肺泡单核细胞在非炎症肺中的募集，但在炎症条件下(JE/MCP-1/LPS沉积)，Ram在很大程度上促进了肺泡细胞因子反应和早期中性粒细胞和延迟单核细胞内流。在这些条件下观察到的肺屏障功能的丧失是独立于RAM的，但涉及到通过β(2)-整合素参与的中性粒细胞循环。
Intratracheal instillation of the monocyte chemoattractant JE/monocyte chemoattractant protein (MCP)-1 in mice was recently shown to cause increased alveolar monocyte accumulation in the absence of lung inflammation, whereas combined JE/MCP-1/lipopolysaccharide (LPS) challenge provoked acute lung inflammation with early alveolar neutrophil and delayed alveolar monocyte influx. We evaluated the role of resident alveolar macrophages (rAM) in these leukocyte recruitment events and related phenomena of lung inflammation. Depletion of rAM by pretreatment of mice with liposomal clodronate did not affect the JE/MCP-1-driven alveolar monocyte accumulation, despite the observation that rAM constitutively expressed the JE/MCP-1 receptor CCR2, as analyzed by flow cytometry and immunohistochemistry. In contrast, depletion of rAM largely suppressed alveolar cytokine release as well as neutrophil and monocyte recruitment profiles upon combined JE/MCP-1/LPS treatment. Despite this strongly attenuated alveolar inflammatory response, increased lung permeability was still observed in rAM-depleted mice undergoing JE/MCP-1/LPS challenge. Lung leakage was abrogated by codepletion of circulating neutrophils or administration of anti-CD18. Collectively, rAM are not involved in JE/MCP-1-driven alveolar monocyte recruitment in noninflamed lungs but largely contribute to the alveolar cytokine response and enhanced early neutrophil and delayed monocyte influx under inflammatory conditions (JE/MCP-1/LPS deposition). Loss of lung barrier function observed under these conditions is rAM independent but involves circulating neutrophils via beta(2)-integrin engagement.