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干扰素诱导的与高尔基体和内质网相关的47 kDa GTP酶IIGP在李斯特菌病期间短暂表达。

The IFN-inducible Golgi- and endoplasmic reticulum- associated 47-kDa GTPase IIGP is transiently expressed during listeriosis.

作者信息

Zerrahn Jens, Schaible Ulrich E, Brinkmann Volker, Guhlich Ute, Kaufmann Stefan H E

机构信息

Department of Immunology and Core Facility Microscopy, Max Planck Institute for Infectionbiology, Berlin, Germany.

出版信息

J Immunol. 2002 Apr 1;168(7):3428-36. doi: 10.4049/jimmunol.168.7.3428.

Abstract

Members of the 47-kDa GTPase family are implicated in an IFN-gamma-induced, as yet unclear, mechanism that confers innate resistance against infection with intracellular pathogens. Overt immunological parameters are apparently uncompromised in mice deficient for individual members and the prototype of this family, IGTP, localizes to the endoplasmic reticulum. This suggests that these GTPases are involved in intracellular defense. We analyzed the expression of the 47-kDa GTPase cognate, IIGP, in splenic sections from mice infected with the intracellular pathogen Listeria monocytogenes by immunohistochemistry. An early transient IIGP induction was observed revealing the IFN-gamma responsiveness of cellular subcompartments within the spleen in early listeriosis. Marginal metallophilic macrophages and endothelial cells within the red and white pulp strongly expressed IIGP, while other splenocytes remained negative. In vitro analyses show that both type I and type II IFNs are prime stimuli for IIGP induction in various cells, including L. monocytogenes-infected or LPS-stimulated macrophages, endothelial cells, and activated T cells. Contrary to the subcellular localization of IGTP, IIGP was predominantly associated with the Golgi apparatus and also localizes to the endoplasmic reticulum. We conclude that IIGP exerts a distinct role in IFN-induced intracellular membrane trafficking or processing.

摘要

47-kDa GTP酶家族成员参与一种由γ干扰素诱导的、机制尚不清楚的过程,该过程赋予机体对细胞内病原体感染的天然抵抗力。对于该家族单个成员缺陷的小鼠,明显的免疫参数并未受损,且该家族的原型IGTP定位于内质网。这表明这些GTP酶参与细胞内防御。我们通过免疫组织化学分析了感染细胞内病原体单核细胞增生李斯特菌的小鼠脾脏切片中47-kDa GTP酶同源物IIGP的表达。观察到早期短暂的IIGP诱导,揭示了早期李斯特菌病中脾脏内细胞亚群对γ干扰素的反应性。红髓和白髓内的边缘亲金属巨噬细胞和内皮细胞强烈表达IIGP,而其他脾细胞仍为阴性。体外分析表明,I型和II型干扰素都是多种细胞中IIGP诱导的主要刺激因素,包括单核细胞增生李斯特菌感染或脂多糖刺激的巨噬细胞、内皮细胞和活化的T细胞。与IGTP的亚细胞定位相反,IIGP主要与高尔基体相关,也定位于内质网。我们得出结论,IIGP在干扰素诱导的细胞内膜运输或加工中发挥独特作用。

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