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Effects of Anaplasma phagocytophilum on Host Cell Ferritin mRNA and Protein Levels

机译：吞噬嗜浆细胞对宿主细胞铁蛋白mRNA和蛋白水平的影响

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Ferritin is a major intracellular iron storage protein and also functions as a cytoprotectant by sequestering iron to minimize the formation of reactive oxygen species. Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, is an obligate intracellular bacterium that colonizes neutrophils. We have previously reported that human promyelocytic HL-60 cells infected with A. phagocytophilum demonstrate increased transcription of ferritin heavy chain and also that the bacterium stimulates neutrophil NADPH oxidase assembly and degranulation during the initial hours of infection (J. A. Carlyon, W. T. Chan, J. Galan, D. Roos, and E. Fikrig, J. Immunol. >169:7009-7018, 2002, and J. A. Carlyon, D. Abdel-Latif, M. Pypaert, P. Lacy, and E. Fikrig, Infect. Immun. 72:4772-4783, 2004). In this study, we assessed ferritin mRNA and protein levels during A. phagocytophilum infection in vitro using HL-60 cells and neutrophils and in vivo using neutrophils from infected mice. The addition of A. phagocytophilum, as well as Escherichia coli and serum-opsonized zymosan, to neutrophils results in a pronounced increase in ferritin light-chain transcription and a concomitant rise in ferritin protein levels. Neutrophils from A. phagocytophilum-infected mice demonstrate elevated ferritin heavy-chain mRNA expression, a phenomenon consistent with infections by intracellular pathogens. Notably, ferritin protein levels of infected HL-60 cells were markedly diminished in a dose- and time-dependent manner. These studies provide insight into the effects A. phagocytophilum has on the ferritin levels of its host cell.
机译：铁蛋白是主要的细胞内铁存储蛋白，并且通过螯合铁以最小化活性氧的形成，还起细胞保护剂的作用。人类粒细胞无性病的病原体 phaphacytophilum 是一种专营于细胞的细菌，它在嗜中性粒细胞中定殖。先前我们曾报道过人类 A感染了人类早幼粒细胞HL-60细胞。 phagocytophilum 证明了铁蛋白重链的转录增加，并且该细菌在感染的最初几个小时内刺激中性粒细胞NADPH氧化酶的组装和脱粒（JA Carlyon，WT Chan，J。Galan，D。Roos和E. Fikrig J. Immunol。> 169： 7001-7018，2002年，以及JA Carlyon，D.Abdel-Latif，M.Pypaert，P.Lacy和E.Fikrig，Infect.Immun.72：4772- 4783，2004）。在这项研究中，我们评估了 A期间铁蛋白的mRNA和蛋白质水平。 HL-60细胞和嗜中性粒细胞在体外进行噬菌体感染，而感染小鼠的嗜中性粒细胞在体内进行吞噬。 A的添加。嗜中性粒细胞吞噬吞噬细胞，大肠杆菌和血清调理的酵母聚糖，导致铁蛋白轻链转录明显增加，铁蛋白蛋白水平随之升高。来自 A的嗜中性粒细胞感染了吞噬细胞的小鼠表现出铁蛋白重链mRNA表达升高，这种现象与细胞内病原体的感染一致。值得注意的是，感染的HL-60细胞的铁蛋白蛋白水平以剂量和时间依赖性方式显着降低。这些研究提供了对 A的影响的见解。吞噬细胞具有其宿主细胞中铁蛋白的水平。

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