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目的观察间日疟原虫代谢产物疟色素(HZ)对树突状细胞(DC)成熟分化的影响。方法以间日疟患者感染红细胞获得间日疟原虫制备纯化HZ,体外刺激人单核来源的未成熟DC。采用流式细胞术分析0.1、1.0、10.0μmol/L不同浓度的HZ作用下DC成熟相关分子CD83、CD86、HLA-DR的表达变化;同时观察DC在HZ刺激后再经脂多糖(LPS)诱导其上述分子的表达变化。结果 0.1、1.0、10.0μmol/L的HZ刺激的DC表达CD83、CD86和HLA-DR阳性百分率均低于LPS诱导组(P均<0.05);1.0、10.0μmol/L的HZ刺激组的CD83、CD86和HLA-DR明显低于未刺激组(P均<0.05);HZ1.0、10.0μmol/L组HLA-DR的表达低于HZ0.1μmol/L组(P均<0.05)。与未刺激组DC相比,HZ0.1μmol/L+LPS组DC的CD83表达明显升高(P<0.01),CD86表达明显升高(P<0.05),HZ1.0μmol/L+LPS组的CD83明显升高(P<0.01);HZ10.0μmol/L+LPS组CD86表达与HZ0.1μmol/L+LPS和HZ1.0μmol/L+LPS组相比明显降低(P均<0.05)。结论间日疟原虫来源的HZ能导致DC的CD83、CD86和HLA-DR表达下调,但负载HZ的DC仍可以在LPS等诱导剂作用下部分上调这些成熟相关分子的表达。HZ对DC的成熟性分化具有剂量依赖性抑制的特征。DC对HZ的过度吞噬而导致成熟抑制可能是疟原虫逃逸免疫攻击的重要方式之一。
Objective To observe the effect of Plasmodium vivax malaria pigment (HZ) on the maturation and differentiation of dendritic cells (DCs). Methods Purified HZ was prepared by infecting erythrocytes with Plasmodium vivax and purifying immature DC derived from human mononuclear cells. Flow cytometry was used to analyze the expression of DC maturation-related molecules CD83, CD86 and HLA-DR under the stimulation of 0.1,1.0,10.0μmol / L HZ. Meanwhile, DCs were induced by LPS after HZ stimulation The expression of these molecules changes. Results The percentages of positive expression of CD83, CD86 and HLA-DR in HZ-stimulated DCs of 0.1, 1.0 and 10.0μmol / L groups were lower than those of LPS group (all P <0.05) The expression of HLA-DR was lower in HZ1.0 and 10.0μmol / L groups than in HZ0.1μmol / L group (P <0.05). Compared with unstimulated DCs, CD83 expression was significantly increased (P <0.01) and CD86 expression was significantly increased in HZ0.1μmol / L + LPS group (P <0.05) (P <0.01). CD86 expression in HZ10.0μmol / L + LPS group was significantly lower than that in HZ0.1μmol / L + LPS group and HZ1.0μmol / L + LPS group (all P <0.05). Conclusions HZ derived from Plasmodium vivax can result in the down-regulation of CD83, CD86 and HLA-DR expression in DCs. However, DCs loaded with HZ can partially up-regulate the expression of these mature-related molecules under the induction of LPS. HZ has a dose-dependent inhibition of DC maturation. Mature inhibition of HZ by phagocytosis of HZ by DC may be one of the important ways of immune escape from Plasmodium.