The critical role of hematopoietic cells in lipopolysaccharide-induced airway inflammation
The critical role of hematopoietic cells in lipopolysaccharide-induced airway inflammation
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DOI：
10.1164/rccm.200407-953oc
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发表时间：
2005-04-15
影响因子：
24.7
通讯作者：
Schwartz, DA
中科院分区：
文献类型：
--
作者：
Hollingsworth, JW;Chen, BJ;Schwartz, DA
在LPS的作用下，中性粒细胞迅速和选择性地进入空气空间，促进了细菌病原体的清除。然而，中性粒细胞浸润也可参与环境性气道疾病的发生和进展。先前的数据显示，在吸入或全身给药大肠杆菌LPS后，toll样受体4 （tlr4）是中性粒细胞向肺募集所必需的。虽然许多细胞类型表达tlr4，但内皮细胞表达tlr4是特异性需要的，以隔离肺中的中性粒细胞，以应对全身内毒素。为了确定吸入LPS后中性粒细胞募集需要trl4表达的细胞类型，我们分别在造血细胞和肺结构细胞上生成了表达tlr4的嵌合小鼠。在接受野生型骨髓的tlr4缺陷小鼠中，中性粒细胞向空区募集完全恢复。相比之下，接受tlr1缺陷骨髓的野生型动物的中性粒细胞募集显著减少。此外，野生型肺泡巨噬细胞的过继转移也恢复了tlr4缺陷受体小鼠向肺募集中性粒细胞的能力。这些数据表明造血细胞和肺泡巨噬细胞在启动lps诱导的中性粒细胞从血管空间向空气空间募集中的关键作用。
Rapid and selective recruitment of neutrophils into the airspace in response to LPS facilitates the clearance of bacterial pathogens. However, neutrophil infiltration can also participate in the development and progression of environmental airway disease. Previous data have revealed that Toll-like receptor 4 (tlr4) is required for neutrophil recruitment to the lung after either inhaled or systemically administrated LPS from Escherichia coli. Although many cell types express tlr4, endothelial cell expression of tlr4 is specifically required to sequester neutrophils in the lung in response to systemic endotoxin. To identify the cell types requiring trl4 expression for neutrophil recruitment after inhaled LPS, we generated chimeric mice separately expressing tlr4 on either hematopoietic cells or on structural lung cells. Neutrophil recruitment into the airspace was completely restored in tlr4-deficient mice receiving wild-type bone marrow. By contrast, wild-type animals receiving tlr4-deficient marrow had dramatically reduced neutrophil recruitment. Moreover, adoptive transfer of wild-type alveolar macrophages also restored the ability of tlr4-deficient recipient mice to recruit neutrophils to the lung. These data demonstrate the critical role of hematopoietic cells and alveolar macrophages in initiating LPS-induced neutrophil recruitment from the vascular space to the airspace.