Inhibition of intracellular bacterial replication in fibroblasts is dependent on the perforin-like protein (perforin-2) encoded by macrophage-expressed gene 1.
Inhibition of intracellular bacterial replication in fibroblasts is dependent on the perforin-like protein (perforin-2) encoded by macrophage-expressed gene 1.
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抑制成纤维细胞中细胞内细菌复制的抑制取决于巨噬细胞表达的基因1所编码的穿孔蛋白样蛋白（Perforin-2）。
DOI：
10.1159/000345249
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发表时间：
2013
影响因子：
5.3
通讯作者：
Podack ER
中科院分区：
文献类型：
--
作者：
McCormack R;de Armas LR;Shiratsuchi M;Ramos JE;Podack ER
众所周知，成纤维细胞可以消除细胞内细菌，但其杀菌机制的致命打击尚未确定。我们发现，干扰素或细胞内细菌感染可以诱导初级胚胎和已建立的成纤维细胞表达穿孔素样 mRNA，之前称为巨噬细胞表达基因 1 (mpeg1)。穿孔素样 mRNA 的存在和水平与原代小鼠胚胎成纤维细胞 (MEF) 消除细胞内细菌的能力相关。此外，穿孔素样分子的 siRNA 敲除消除了杀菌活性并允许细胞内细菌复制。 MEF 的补充（其中内源性穿孔素样分子已被 RFP 标记版本敲除）可恢复杀菌活性。穿孔素样分子对致病菌和非致病菌（包括革兰氏阳性菌、革兰氏阴性菌和耐酸菌）具有广泛的杀菌特异性。穿孔素样分子使得先前对溶菌酶具有抗性的细菌对溶菌酶的裂解敏感，这表明穿孔素样蛋白对外细胞壁造成物理损伤。 MEF 通过穿孔素样蛋白的插入、聚合和孔形成来损伤细胞内细菌的细胞壁，类似于补体和溶细胞淋巴细胞的穿孔素-1 的孔形成剂。我们建议将其命名为 Perforin-2。
Fibroblasts are known to eliminate intracellular bacteria, but the lethal hit of the bactericidal mechanism has not been defined. We show that primary embryonic and established fibroblasts can be induced by interferons or by intracellular bacterial infection to express a perforin-like mRNA previously described as macrophage expressed gene 1 (mpeg1). The presence and level of the perforin-like mRNA correlate with the ability of primary mouse embryonic fibroblasts (MEF) to eliminate intracellular bacteria. In addition, siRNA knock-down of the perforin-like molecule abolishes bactericidal activity and allows intracellular bacterial replication. Complementation of MEF in which the endogenous perforin-like molecule has been knocked down with an RFP-tagged version restores bactericidal activity. The perforin-like molecule has broad bactericidal specificity for pathogenic and non-pathogenic bacteria including Gram positive, Gram negative and acid fast bacteria. The perforin-like molecule renders previously lysozyme-resistant bacteria sensitive to lysis by lysozyme suggesting physical damage of the outer cell wall by the perforin-like protein. MEFs damage cell walls of intracellular bacteria by insertion, polymerization and pore-formation of the perforin-like protein, analogous to pore-formers of complement and Perforin-1 of cytolytic lymphocytes. We propose the name Perforin-2.
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DOI：
10.1084/jem.149.4.870
发表时间：
1979-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Schreiber RD;Morrison DC;Podack ER;Müller-Eberhard HJ
通讯作者：
Müller-Eberhard HJ
DOI：
10.1073/pnas.0501701102
发表时间：
2005-04-05
影响因子：
11.1
作者：
Wan, YSY;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
64.8
作者：
KAGI, D;LEDERMANN, B;HENGARTNER, H
通讯作者：
HENGARTNER, H
影响因子：
64.8
作者：
PODACK, ER;DENNERT, G
通讯作者：
DENNERT, G
影响因子：
4.7
作者：
Wang, Guo-Dong;Zhang, Ke-Feng;Wang, Yi-Lei
通讯作者：
Wang, Yi-Lei