Role of G protein-coupled receptor kinase-6 in Escherichia coli lung infection model in mice.
Role of G protein-coupled receptor kinase-6 in Escherichia coli lung infection model in mice.
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DOI：
10.1152/physiolgenomics.00066.2017
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发表时间：
2017-11
影响因子：
4.6
通讯作者：
Taehyung Lee;N. Packiriswamy;E. Lee;P. C. Lucas;L. McCabe;N. Parameswaran
中科院分区：
文献类型：
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作者：
Taehyung Lee;N. Packiriswamy;E. Lee;P. C. Lucas;L. McCabe;N. Parameswaran
G蛋白偶联受体激酶-6（GRK 6）是一种丝氨酸/苏氨酸激酶，在炎症过程中起重要作用。在这项研究中，我们使用GRK 6敲除（KO）和野生型（WT）小鼠研究了GRK 6在大肠杆菌诱导的肺部感染和炎症中的作用。肠内滴注E.与WT小鼠相比，KO小鼠支气管肺泡灌洗（BAL）中的细菌负荷显著增加。KO小鼠中细菌清除率降低不是由于中性粒细胞吞噬或杀伤的内在缺陷，而是由于KO BAL中中性粒细胞数量减少。有趣的是，与WT小鼠相比，KO小鼠肺中的中性粒细胞数量增加，表明中性粒细胞从肺到支气管肺泡间隙的跨上皮迁移可能功能障碍。这种效应对肺组织具有选择性，因为腹膜感染后两种基因型之间的腹膜中性粒细胞数量相似。尽管WT和KO之间的中性粒细胞CXCR 2/CXCR 3表达相似，但KO小鼠中的IL-17 A表达高于WT小鼠。这些结果表明，KO肺中的中性粒细胞计数增加，但BAL中的数量减少可能是由于跨上皮迁移缺陷和/或改变的趋化因子/细胞因子。总之，我们的研究表明GRK 6在细菌感染期间特异性肺组织中性粒细胞迁移中的先前未被认识的和新的作用。
G protein-coupled receptor kinase-6 (GRK6) is a serine/threonine kinase that is important in inflammatory processes. In this study, we examined the role of GRK6 in Escherichia coli-induced lung infection and inflammation using GRK6 knockout (KO) and wild-type (WT) mice. Intratracheal instillation of E. coli significantly enhanced bacterial load in the bronchoalveolar lavage (BAL) of KO compared with WT mice. Reduced bacterial clearance in the KO mice was not due to an intrinsic defect in neutrophil phagocytosis or killing but as a result of reduced neutrophil numbers in the KO BAL. Interestingly, neutrophil numbers in the lung were increased in the KO compared with WT mice, suggesting a potential dysfunction in transepithelial migration of neutrophils from the lungs to the bronchoalveolar space. This effect was selective for lung tissue because peritoneal neutrophil numbers were similar between the two genotypes following peritoneal infection. Although neutrophil expression of CXCR2/CXCR3 was similar between WT and KO, IL-17A expression was higher in the KO compared with WT mice. These results suggest that enhanced neutrophil count in the KO lungs but reduced numbers in BAL are likely due to transepithelial migration defect and/or altered chemokines/cytokines. Together, our studies suggest a previously unrecognized and novel role for GRK6 in neutrophil migration specific to pulmonary tissue during bacterial infection.