Critical role of endothelial CXCR2 in LPS-induced neutrophil migration into the lung
Critical role of endothelial CXCR2 in LPS-induced neutrophil migration into the lung
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DOI：
10.1172/jci27009
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发表时间：
2006-03-01
影响因子：
15.9
通讯作者：
Ley, K
中科院分区：
文献类型：
--
作者：
Reutershan, J;Morris, MA;Ley, K
在急性肺损伤模型中，CXC趋化因子受体2 （CXCR2）介导多形核白细胞（PMNs）向肺的迁移。由于CXCR2配体（包括CXCL1和CXCL2/3）对pmn具有趋化性，因此CXCR2被认为通过诱导趋化迁移来招募pmn。在PMN向肺募集的模型中，雾化吸入细菌LPS诱导野生型小鼠的PMN向肺募集，但在交配的CXCK2-/-小鼠中没有。令人惊讶的是，用CXCR2-/- BM重组的致死照射野生型小鼠仍显示约50%的PMN向支气管肺泡灌洗液和肺间质中募集，而用CXCR2-/- BM重组的CXCR2-/-小鼠未显示PMN募集。相反，用野生型BM重组的CXCR2-/-小鼠在PMN募集方面显示出令人惊讶的巨大缺陷，这与CXCR2单独对PMN的作用不一致。通过细胞培养、免疫组织化学、流式细胞术和实时RT-PCR检测CXCR2在肺内皮细胞和支气管上皮细胞上的表达。lps诱导的肺微血管通透性增加（Evans蓝色外渗）需要非造血细胞上的CXCR2。我们的数据揭示了内皮细胞和上皮细胞CXCR2在lfs诱导的PMN募集和肺损伤中的作用，我们认为这是以前未被认识到的。
In models of acute lung injury, CXC chemokine receptor 2 (CXCR2) mediates migration of polymorphonuclear leukocytes (PMNs) into the lung. Since CXCR2 ligands, including CXCL1 and CXCL2/3, are chemotactic for PMNs, CXCR2 is thought to recruit PMNs by inducing chemotactic migration. In a model of PMN recruitment to the lung, aerosolized bacterial LPS inhalation induced PMN recruitment to the lung in wild-type mice, but not in littermate CXCK2-/- mice. Surprisingly, lethally irradiated wild-type mice reconstituted with CXCR2-/- BM still showed about 50% PMN recruitment into bronchoalveolar lavage fluid and into lung interstitium, but CXCR2-/- mice reconstituted with CXCR2-/- BM showed no PMN recruitment. Conversely, CXCR2-/- mice reconstituted with wild-type BM showed a surprisingly large defect in PMN recruitment, inconsistent with a role of CXCR2 on PMNs alone. Cell culture, immunohistochemistry, flow cytometry, and real-time RT-PCR were used to show expression of CXCR2 on pulmonary endothelial and bronchial epithelial cells. The LPS-induced increase in lung microvascular permeability as measured by Evans blue extravasation required CXCR2 on nonhematopoietic cells. Our data revealed what we believe to be a previously unrecognized role of endothelial and epithelial CXCR2 in LFS-induced PMN recruitment and lung injury.