Impaired host defense in mice lacking ONZIN
Impaired host defense in mice lacking ONZIN
复制标题
DOI：
10.4049/jimmunol.178.8.5132
复制
发表时间：
2007-04-15
影响因子：
4.4
通讯作者：
Koller, Beverly H.
中科院分区：
文献类型：
--
作者：
Ledford, Julie G.;Kovarova, Martina;Koller, Beverly H.
ONZIN是一种小的、富含半胱氨酸的肽，具有独特的结构，迄今为止在所有脊椎动物中都是保守的。我们发现ONZIN在肠道上皮细胞、肺和免疫系统细胞（包括巨噬细胞和粒细胞）中高水平表达。由于这种表达模式暗示了先天免疫功能的作用，我们产生了缺乏这种蛋白的小鼠，并检查了它们对感染因子的反应能力。Onzin（-/-）小鼠在肺炎克雷伯菌诱导急性腹膜炎后表现出增强的先天免疫反应。这种反应的增加与Onzin（-/-）小鼠细菌负担的增加是一致的。体外研究表明，尽管吞噬作用在Onzin（-/-）中性粒细胞中没有改变，但缺乏这种蛋白的吞噬细胞杀死细菌的效率较低。该结果确定ONZIN是一类新的细胞内蛋白，需要中性粒细胞在吸收细菌后发挥最佳功能。
ONZIN is a small, cysteine-rich peptide of unique structure that is conserved in all vertebrates examined to date. We show-that ONZIN is expressed at high levels in epithelial cells of the intestinal tract, the lung, and in cells of the immune system including macrophages and granulocytes. Because this pattern of expression is suggestive of a role in innate immune function, we have generated mice lacking this protein and examined their ability to respond to challenge with infectious agents. Onzin(-/-) mice show a heightened innate immune response after induction of acute peritonitis with Klebsiella pneumoniae. This increased response is consistent with an increased bacterial burden in the Onzin(-/-) mice. Ex vivo studies show that, whereas phagocytosis is not altered in Onzin(-/-) neutrophils, phagocytes lacking this protein kill bacteria less effectively. This result identifies ONZIN as a novel class of intracellular protein required for optimal function of the neutrophils after uptake of bacteria.