INVESTIGATIONS INTO THE MOLECULAR-BASIS OF MENINGOCOCCAL TOXICITY FOR HUMAN ENDOTHELIAL AND EPITHELIAL-CELLS - THE SYNERGISTIC EFFECT OF LPS AND PILI

INVESTIGATIONS INTO THE MOLECULAR-BASIS OF MENINGOCOCCAL TOXICITY FOR HUMAN ENDOTHELIAL AND EPITHELIAL-CELLS - THE SYNERGISTIC EFFECT OF LPS AND PILI
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DOI:
10.1016/s0882-4010(95)90085-3
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发表时间:
1995-02-01
影响因子:
3.8
通讯作者:
MOXON, ER
MOXON, ER
中科院分区:
医学3区
文献类型:
--
作者:
DUNN, KLR;VIRJI, M;MOXON, ER

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使用人脐静脉内皮细胞作为体外毒性模型,发现脑膜炎奈瑟菌、淋病奈瑟菌、内酰胺奈瑟菌和干燥奈瑟菌对这些细胞造成损伤,而B型流感嗜血杆菌则没有细胞毒性。N.还发现脑膜炎对人类上皮细胞有毒。脑膜炎奈瑟氏菌的主要毒性因子是外膜囊泡的热稳定成分,并可被多粘菌素B抑制,表明脂多糖在毒性中起主要作用。然而,由脂多糖介导的毒性被菌毛依赖性粘附显著调制。菌株内变异体表达改变菌毛蛋白,表现出不同水平的粘附上皮细胞和内皮细胞被用来研究菌毛的作用。观察到的毒性程度与其对培养细胞的相对粘附水平相关。相比之下,依赖于Ope的增加的粘附并没有导致对内皮细胞的毒性增加,这表明丸剂具有协同作用,有助于整体损伤。
Using human umbilical vein endothelial cells as an in vitro model of toxicity, it was found that Neisseria meningitidis, Neisseria gonorrhoeae, Neisseria lactamica and Neisseria sicca caused damage to these cells, in contrast to the lack of cytotoxicity exhibited by Haemophilus influenzae type b. N. meningitidis was also found to be toxic for human epithelial cells. The major toxic factor of N, meningitidis was found to be a heat-stable component of outer membrane vesicles, and could be inhibited by polymyxin B, suggesting that lipopolysaccharide plays a major role in toxicity. However, the toxicity mediated by lipopolysaccharide was modulated significantly by pilus-dependent adherence. Intra-strain variants expressing altered pilins which exhibited different levels of adherence to epithelial and endothelial cells were used to study the role of pilus. The degree of toxicity observed correlated with their relative level of adherence to cultured cells. In contrast, Ope-dependent increased adherence did not result in increased toxicity for endothelial cells, suggesting that pill have a synergistic effect, contributing to the overall damage.