Helicobacter pylori urease binds to class II MHC on gastric epithelial cells and induces their apoptosis
Helicobacter pylori urease binds to class II MHC on gastric epithelial cells and induces their apoptosis
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DOI：
10.4049/jimmunol.165.4.1918
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发表时间：
2000-08-15
影响因子：
4.4
通讯作者：
Reyes, VE
中科院分区：
文献类型：
--
作者：
Fan, XJ;Gunasena, H;Reyes, VE
幽门螺杆菌感染导致胃上皮损伤和包括CD4(+) T细胞在内的细胞浸润。幽门螺杆菌与胃上皮细胞II类MHC分子结合并诱导其凋亡，由于脲酶是幽门螺杆菌表达的丰富蛋白，我们研究了它是否具有与II类MHC结合并诱导II类MHC细胞凋亡的能力。流式细胞术显示pe偶联脲酶与II类MHC+胃上皮细胞系结合。抗II类MHC抗体和葡萄球菌肠毒素b降低了脲酶与人胃上皮细胞的结合。当脲酶与hla - dr1转染的COS-1 （1D12）细胞结合时，证实了脲酶与II类MHC的结合，而与未转染的COS-1细胞不结合。脲酶也与表达多种II类MBC等位基因的B细胞系结合。重组脲酶可诱导表达ⅱ类MHC分子的胃上皮细胞凋亡，但对ⅱ类MHC-细胞无诱导作用。此外，来自抗II类MHC的Fab，而不是来自同型对照抗体的Fab，以浓度依赖的方式阻断脲酶诱导的细胞凋亡。脲酶的黏附特性可能提示幽门螺杆菌脲酶在幽门螺杆菌感染发病机制中具有新的重要作用。
Infection by Helicobacter pylori leads to injury of the gastric epithelium and a cellular infiltrate that includes CD4(+) T cells. H, pylori binds to class II MHC molecules on gastric epithelial cells and induces their apoptosis,Because urease is an abundant protein expressed by H, pylori, we examined whether it had the ability to bind class II MHC and induce apoptosis in class II MHC-bearing cells. Flow cytometry revealed the binding of PE-conjugated urease to class II MHC+ gastric epithelial cell lines. The binding of urease to human gastric epithelial cells was reduced by anti-class II MHC Abs and by staphylococcal enterotoxin B. The binding of urease to class II MHC was confirmed when urease bound to HLA-DR1-transfected COS-I (1D12) cells but not to untransfected COS-1 cells. Urease also bound to a panel of B cell lines expressing various class II MBC alleles. Recombinant urease induced apoptosis in gastric epithelial cells that express class II MHC molecules, but not in class II MHC- cells. Also, Fab from anti-class II MHC and not from isotype control Abs blocked the induction of apoptosis by urease in a concentration-dependent manner. The adhesin properties of urease might point to a novel and important role of H, pylori urease in the pathogenesis of H, pylori infection.