Granulocyte Research Laboratory, Rigshospitalet, Copenhagen, Denmark.
Respir Res. 2010 Jul 15;11(1):96. doi: 10.1186/1465-9921-11-96.
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.
脂氧素 2 是一种抑菌蛋白，可与铁载体结合，铁载体是大肠杆菌（E. coli）产生的一种螯合铁的分子，对细菌生长至关重要。尽管经常接触这种共生细菌，但肺部感染大肠杆菌却很少见。脂氧素 2 是先天免疫系统的效应分子，因此可能在阻止大肠杆菌在肺部生长方面发挥作用。
用两种大肠杆菌菌株感染脂氧素 2 敲除和野生型小鼠。感染后 48 小时取出肺脏，通过免疫组织化学染色和 Western blot 检测肺脏中的脂氧素 2 和 MMP9（一种髓样标记蛋白）。在感染后 2 天和 5 天评估小鼠肺脏中的细菌数量，并监测小鼠 5 天内的死亡率。还研究了同时给予铁载体（一种不能与脂氧素 2 结合的铁源）对大肠杆菌的影响。
将大肠杆菌气管内注入小鼠后，支气管上皮细胞和肺泡 II 型上皮细胞中脂氧素 2 的表达明显增强。髓样细胞向感染部位的迁移也导致肺脏中脂氧素 2 水平升高。感染大肠杆菌后 2 天和 5 天，脂氧素 2 敲除小鼠肺脏中的细菌数量明显高于野生型小鼠（p < 0.05）。此外，感染后 5 天，存活的脂氧素 2 敲除小鼠的脾脏中大肠杆菌数量高于相应的野生型小鼠（p < 0.05）。野生型小鼠对大肠杆菌感染的保护作用可被铁载体 ferrichrome 抵消，表明脂氧素 2 的保护作用取决于其螯合铁的能力。
脂氧素 2 对保护气道免受大肠杆菌感染很重要。
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