Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli infection but not to ischemia-reperfusion injury
Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli infection but not to ischemia-reperfusion injury
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DOI：
10.1073/pnas.0510847103
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发表时间：
2006-02-07
影响因子：
11.1
通讯作者：
Mak, TW
中科院分区：
文献类型：
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作者：
Berger, T;Togawa, A;Mak, TW
已报道脂质运载蛋白2具有多种功能。为了在体内研究这些功能，我们构建了基因靶向的脂质运载蛋白2缺陷型小鼠（Lcn2（-/-）小鼠）。体外研究表明，脂质运载蛋白2对于白细胞介素 - 3（IL - 3）撤离诱导的细胞凋亡以及胚胎发生过程中肾脏分化的诱导很重要。对Lcn2（-/-）小鼠的分析显示，在IL - 3撤离时细胞死亡正常，肾脏发育也正常。然而，我们发现Lcn2（-/-）小鼠对细菌感染的易感性增加，这与所提出的脂质运载蛋白2在铁螯合中的功能相符。从Lcn2（-/-）小鼠中分离出的中性粒细胞与野生型（WT）对照相比，抑菌活性显著降低。添加外源铁可消除野生型中性粒细胞的抑菌特性，这表明脂质运载蛋白2在抗菌先天免疫反应中的主要功能是限制这种必需元素。脂质运载蛋白2的另一个重要功能是其对肾脏缺血 - 再灌注损伤的保护作用。我们使用严重肾衰竭小鼠模型分析Lcn2（-/-）小鼠，未发现与野生型同窝小鼠相比有任何显著差异。
Diverse functions have been reported for lipocalin 2. To investigate these functions in vivo, we generated gene-targeted lipocalin 2-deficient mice (Lcn2(-/-) mice). In vitro studies have suggested that lipocalin 2 is important for cellular apoptosis induced by IL-3 withdrawal, and for the induction of kidney differentiation during embryogenesis. Analysis of Lcn2(-/-) mice showed normal cell death upon IL-3 withdrawal and normal kidney development. However, we found that Lcn2(-/-) mice exhibited an increased susceptibility to bacterial infections, in keeping with the proposed function of lipocalin 2 in iron sequestration. Neutrophils isolated from Lcn2(-/-) mice showed significantly less bacteriostatic activity compared with WT controls. The bacteriostatic property of the WT neutro-phils was abolished by the addition of exogenous iron, indicating that the main function of lipocalin 2 in the antibacterial innate immune response is to limit this essential element. Another important function ascribed to lipocalin 2 has been its protective role against kidney ischemia-reperfusion injury. We analyzed Lcn2(-/-) mice using a mouse model for severe renal failure and could not detect any significant differences compared with their WT littermates.