Naschberger Elisabeth, Lubeseder-Martellato Clara, Meyer Nadine, Gessner Ruth, Kremmer Elisabeth, Gessner Andrè, Stürzl Michael
Department of Surgery, Division of Molecular and Experimental Surgery, Institute for Clinical Microbiology, Immunology, and Hygiene, Munich, Germany.
Am J Pathol. 2006 Sep;169(3):1088-99. doi: 10.2353/ajpath.2006.060244.
Interferon-gamma-induced GTPases are key to the protective immunity against microbial and viral pathogens. As yet, the cell interior has been regarded as the exclusive residence of these proteins. Here we show that a member of this group, human guanylate binding protein-1 (hGBP-1), is secreted from cells. Secretion occurred in the absence of a leader peptide via a nonclassical, likely ABC transporter-dependent, pathway, was independent of hGBP-1 GTPase activity and isoprenylation, and did not require additional interferon-gamma-induced factors. Interestingly, hGBP-1 was only secreted from endothelial cells but not from any of the nine different cell types tested. Clinically most important was the detection of significantly (P<0.001, Mann-Whitney U-test) increased hGBP-1 concentrations in the cerebrospinal fluid of patients with bacterial meningitis (n=32) as compared to control patients (n=74). In this first report of a secreted GTPase, we demonstrate that secreted hGBP-1 may be a useful surrogate marker for diagnosis of bacterial meningitis.
干扰素γ诱导的GTP酶是抵御微生物和病毒病原体的保护性免疫的关键。迄今为止，细胞内部一直被视为这些蛋白质的唯一存在场所。在此我们表明，该蛋白家族的一个成员，即人鸟苷酸结合蛋白1（hGBP-1），可从细胞中分泌出来。分泌是通过非经典途径（可能依赖ABC转运蛋白）在没有前导肽的情况下发生的，与hGBP-1的GTP酶活性和异戊二烯化无关，并且不需要其他干扰素γ诱导因子。有趣的是，hGBP-1仅从内皮细胞分泌，而在所测试的九种不同细胞类型中均未分泌。临床上最重要的是，与对照患者（n = 74）相比，细菌性脑膜炎患者（n = 32）脑脊液中的hGBP-1浓度显著升高（P<0.001，曼-惠特尼U检验）。在关于分泌型GTP酶的这篇首次报道中，我们证明分泌的hGBP-1可能是诊断细菌性脑膜炎的有用替代标志物。
