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Mannose Induces the Release of Cytopathic Factors from Acanthamoeba castellanii

机译:甘露糖诱导从棘阿米巴castellanii细胞因子释放。

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Acanthamoeba keratitis is a chronic inflammatory disease of the cornea which is highly resistant to many antimicrobial agents. The pathogenic mechanisms of this disease are poorly understood. However, it is believed that the initial phases in the pathogenesis of Acanthamoeba keratitis involve parasite binding and lysis of the corneal epithelium. These processes were examined in vitro, usingAcanthamoeba castellanii trophozoites. Parasites readily adhered to Chinese hamster corneal epithelial cells in vitro; however, parasite binding was strongly inhibited by mannose but not by lactose. Although mannose prevented trophozoite binding, it did not affect cytolysis of corneal epithelial cells. Moreover, mannose treatment induced trophozoites to release cytolytic factors that lysed corneal epithelial cells in vitro. These factors were uniquely induced by mannose because supernatants collected from either untreated trophozoites or trophozoites treated with other sugars failed to lyse corneal cells. The soluble factors were size fractionated in centrifugal concentrators and found to be ≥100 kDa. Treatment of the supernatants with the serine protease inhibitor phenylmethylsulfonyl fluoride inhibited most, but not all, of the cytopathic activity. These data suggest that the binding ofAcanthamoeba to mannosylated proteins on the corneal epithelium may exacerbate the pathogenic cascade by initiating the release of cytolytic factors.
机译: hamanthamoeba 角膜炎是一种慢性角膜炎性疾病,对许多抗菌药物高度耐药。对该病的致病机理了解甚少。然而,人们相信 Acanthamoeba 角膜炎发病机理的初始阶段涉及寄生虫结合和角膜上皮溶解。使用棘孢棘孢滋养体在体外检查了这些过程。体外,寄生虫容易粘附到中国仓鼠角膜上皮细胞上。然而,甘露糖强烈抑制了寄生虫的结合,而乳糖则没有。尽管甘露糖阻止滋养体结合,但它不影响角膜上皮细胞的细胞溶解。此外,甘露糖处理诱导滋养体释放细胞溶解因子,从而在体外溶解角膜上皮细胞。这些因素是甘露糖唯一诱导的,因为从未经处理的滋养体或经其他糖处理的滋养体收集的上清液无法裂解角膜细胞。在离心浓缩器中对可溶因子进行了大小分级,发现≥100 kDa。用丝氨酸蛋白酶抑制剂苯基甲基磺酰氟处理上清液可抑制大部分但不是全部的细胞病变活性。这些数据表明棘阿米巴与角膜上皮上的甘露糖基化蛋白的结合可能通过引发细胞溶解因子的释放而加剧致病级联反应。

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