Lipocalin 2 is protective against E. coli pneumonia.

Lipocalin 2 is protective against E. coli pneumonia.
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DOI:
10.1186/1465-9921-11-96
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发表时间:
2010-07-15
影响因子:
5.8
通讯作者:
Cowland JB
Cowland JB
中科院分区:
医学2区
文献类型:
--
作者:
Wu H;Santoni-Rugiu E;Ralfkiaer E;Porse BT;Moser C;Høiby N;Borregaard N;Cowland JB

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脂质运载蛋白2是一种结合铁载体肠杆菌素的抑菌蛋白,铁载体肠杆菌素是一种由大肠杆菌产生的铁螯合分子。大肠杆菌)中的蛋白质。E.大肠杆菌是罕见的,尽管经常暴露于这种肠道细菌。脂质运载蛋白2是先天免疫系统的效应分子,因此可能在抑制大肠杆菌生长中发挥作用。肺里的大肠杆菌用两株大肠杆菌感染Lipocalin 2基因敲除小鼠和野生型小鼠。杆菌感染后48小时取出肺,并通过免疫组织化学染色和蛋白质印迹法检查脂质运载蛋白2和MMP 9(骨髓标志物蛋白)。在感染后第2天和第5天评估小鼠肺中的细菌数量,并在五天的时间内监测小鼠的死亡率。还检查了与大肠杆菌一起施用铁色素(不能被脂质运载蛋白2结合的铁源)沿着的效果。E.结果显示,小鼠支气管上皮和肺泡II型细胞中脂质运载蛋白2的表达明显增强。骨髓细胞向感染部位的迁移也有助于肺中脂质运载蛋白2水平的增加。在用E.大肠杆菌(p < 0.05)。此外,E.在感染后第5天,在存活的脂质运载蛋白2敲除小鼠的脾脏中比在相应的野生型小鼠中发现了大肠杆菌(p < 0.05)。对E.野生型小鼠中的大肠杆菌感染可以被铁载体铁色素抵消,这表明脂质运载蛋白2的保护作用取决于其螯合铁的能力。Lipocalin 2对保护气道免受E.杆菌
Lipocalin 2 is a bacteriostatic protein that binds the siderophore enterobactin, an iron-chelating molecule produced by Escherichia coli (E. coli) that is required for bacterial growth. Infection of the lungs by E. coli is rare despite a frequent exposure to this commensal bacterium. Lipocalin 2 is an effector molecule of the innate immune system and could therefore play a role in hindering growth of E. coli in the lungs. Lipocalin 2 knock-out and wild type mice were infected with two strains of E. coli. The lungs were removed 48 hours post-infection and examined for lipocalin 2 and MMP9 (a myeloid marker protein) by immunohistochemical staining and western blotting. Bacterial numbers were assessed in the lungs of the mice at 2 and 5 days after infection and mortality of the mice was monitored over a five-day period. The effect of administering ferrichrome (an iron source that cannot be bound by lipocalin 2) along with E.coli was also examined. Intratracheal installation of E. coli in mice resulted in strong induction of lipocalin 2 expression in bronchial epithelium and alveolar type II pneumocytes. Migration of myeloid cells to the site of infection also contributed to an increased lipocalin 2 level in the lungs. Significant higher bacterial numbers were observed in the lungs of lipocalin 2 knock-out mice on days 2 and 5 after infection with E. coli (p < 0.05). In addition, a higher number of E. coli was found in the spleen of surviving lipocalin 2 knock-out mice on day 5 post-infection than in the corresponding wild-type mice (p < 0.05). The protective effect against E. coli infection in wild type mice could be counteracted by the siderophore ferrichrome, indicating that the protective effect of lipocalin 2 depends on its ability to sequester iron. Lipocalin 2 is important for protection of airways against infection by E. coli.
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