Deficiency of HIF-1α in myeloid cells protects Escherichia coli or LPS-induced acute lung injury
Deficiency of HIF-1α in myeloid cells protects Escherichia coli or LPS-induced acute lung injury
复制标题
骨髓细胞中 HIF-1α 的缺乏可保护大肠杆菌或 LPS 诱导的急性肺损伤
DOI：
10.1093/qjmed/hcy160
复制
发表时间：
2018-10-01
影响因子：
13.3
通讯作者：
Su, X.
中科院分区：
文献类型：
--
作者：
Huang, Y.;Zhao, C.;Su, X.
背景资料：巨噬细胞中缺氧诱导因子-1 α（HIF-1 α）的缺乏降低了脂多糖（LPS）诱导的死亡率;然而，骨髓细胞中HIF-1 α的表达是否有助于大肠杆菌的发育（E. coil）或LPS诱导的急性肺损伤（acute lung injury，ALI）的研究较少。方法：我们用大肠杆菌感染Hif 1 α（fl/fl）和Hif 1 α（fl/fl）LysM（Cre）小鼠，并用ELISA方法检测Hif 1 α（fl/fl）LysM（Cre）和Hif 1 α（fl/fl）LysM（Cre）LysM。大肠杆菌或LPS来分析肺和脾的炎症反应。流式细胞术检测肺、脾α 7 nAChR（+）CD 11b（+）细胞的变化。用Chma 7和Itgam双基因敲除小鼠检测E.结果：髓系细胞Hif 1 α基因缺失可减轻E. coli肺水肿、炎性细胞浸润、肺组织和BAL炎性细胞因子的表达，并能明显减轻LPS诱导的ALI。大肠杆菌诱导的ALI。流式细胞术分析显示，E.线圈攻击的Hif 1 α（fl/fl）LYsM（Cre）小鼠与E.线圈攻击的Hif 1 α（fl/fl）LYsM（Cre）小鼠。Chrna 7和Itgam的双重敲除增加了肺E过程中肺和脾细胞中HIF-1 α的表达。大肠杆菌感染。结论：髓系细胞Hif 1 α基因缺失可通过α 7 nAChR（+）CD 11b（+）细胞和迷走神经回路的神经支配对LPS诱导的肺损伤起到保护作用。
Background: Deficiency of hypoxia-induced factor-1 alpha (HIF-1 alpha) in macrophages reduced lipopolysaccharide (LPS)-induced mortality; however, whether HIF-1 alpha expression in myeloid cells would contribute to the development of Escherichia coli (E. coil) or LPS-induced acute lung injury (ALI) is less investigated.Aim: To test whether deletion of Hif1 alpha in myeloid cells affects E. coil or LPS-induced ALI and to elicit the underlying mechanisms.Design: Laboratory study.Methods: We intratracheally challenged Hif1 alpha(fl/fl) and Hif1 alpha(fl/fl)LysM(Cre) mice with E. coli or LPS to analyze lung and spleen inflammatory responses. Flow cytometry was used to analyze the changes of alpha 7 nAChR(+)CD11b(+) cells in the lung and spleen. Double knockout of Chma7 and Itgam mice were used to examine expression of HIF-1 alpha during E. coli lung infection.Vagotomy was performed to demonstrate the role of vagus nerve in mediating protective effects of deletion of Hif1 alpha in myeloid cells on LPS-induced ALI.Results: Deletion of Hif1 alpha in myeloid cells could reduce lung edema, inflammatory cell infiltration, and lung and BAL inflammatory cytokines in E. coli-induced ALI. Flow cytometric analysis revealed that alpha 7 nAChR(+)CD11b(+) cells in the lung and spleen were markedly increased in E. coil-challenged Hif1 alpha(fl/fl)LYsM(Cre)mice compared with E. coil-challenged Hif1 alpha(fl/fl)LYsM(Cre) mice. Double knockout of Chrna7 and Itgam increased HIF-1 alpha expression in lung and spleen cells during lung E. coli infection. Vagotomy abolished the protective effect of deletion of Hipa in myeloid cells on LPS-induced ALI.Conclusion: Deletion of Hif1 alpha in myeloid cells could protect mice from lung injury depending on alpha 7 nAChR(+)CD11b(+) cells and innervation of vagal circuits.