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首页> 外文期刊>Infection and immunity >High-Affinity Interaction between Gram-Negative Flagellin and a Cell Surface Polypeptide Results in Human Monocyte Activation
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High-Affinity Interaction between Gram-Negative Flagellin and a Cell Surface Polypeptide Results in Human Monocyte Activation

机译：革兰氏阴性鞭毛蛋白和细胞表面多肽之间的高亲和力相互作用导致人类单核细胞激活。

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Flagella from diverse gram-negative bacteria induce tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) synthesis by human monocytes (F. Ciacci-Woolwine, P. F. McDermott, and S. B. Mizel, Infect. Immun. 67:5176–5185, 1999). In this study, we establish that purified flagellin (FliC or FljB), the major filament protein from Salmonella enterica serovar Enteritidis,S. enterica serovar Typhimurium, and Pseudomonas aeruginosa, is an extremely potent inducer of TNF-α production by human monocytes and THP-1 myelomonocytic cells. Fifty percent of maximal TNF-α production (EC50) was obtained with 1.5 × 10?11 M flagellin (0.75 ng/ml). Mutagenesis studies revealed that the central hypervariable region of flagellin is essential for the TNF-α-inducing activity of the protein. Although less active than the wild-type protein, a Salmonellaflagellin mutant composed of only the central hypervariable region retained substantial TNF-α-inducing activity at nanomolar concentrations. In contrast, the conserved amino- and carboxy-terminal regions are inactive. Mutational analysis of the hypervariable region revealed that it contains two equally active TNF-α-inducing domains. The ability of THP-1 cells to respond to purified flagellins is dramatically reduced by mild trypsin treatment of the cells. Taken together, our results demonstrate that the cytokine-inducing activity of flagellins from gram-negative bacteria results from the interaction of these proteins with high-affinity cell surface polypeptide receptors on monocytes.
机译：来自各种革兰氏阴性细菌的鞭毛诱导人单核细胞合成肿瘤坏死因子α（TNF-α）和白介素1β（IL-1β）（F. Ciacci-Woolwine，PF McDermott和SB Mizel，Infect。Immun。67： 5176-5185，1999）。在这项研究中，我们建立了纯化的鞭毛蛋白（FliC或FljB），这是 Salmonella enterica serovar Enteritidis， S的主要丝状蛋白。肠杆菌血清型鼠伤寒杆菌和铜绿假单胞菌是人单核细胞和THP-1骨髓单核细胞产生TNF-α的极强诱导剂。用1.5×10 ？11 M鞭毛蛋白（0.75 ng / ml）获得最大TNF-α产量的50％（EC 50 ）。诱变研究表明，鞭毛蛋白的中央高变区对于该蛋白的TNF-α诱导活性至关重要。尽管其活性不如野生型蛋白，但仅由中​​央高变区组成的沙门氏菌鞭毛蛋白突变体在纳摩尔浓度下仍具有实质性的TNF-α诱导活性。相反，保守的氨基和羧基末端区域是无活性的。高变区的突变分析显示，它包含两个同等活性的TNF-α诱导域。温和的胰蛋白酶处理可显着降低THP-1细胞对纯化鞭毛蛋白的反应能力。两者合计，我们的结果表明，革兰氏阴性细菌鞭毛蛋白的细胞因子诱导活性是这些蛋白质与单核细胞上高亲和力细胞表面多肽受体相互作用的结果。

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