Circulating Red Cell-derived Microparticles in Human Malaria

Circulating Red Cell-derived Microparticles in Human Malaria
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DOI:
10.1093/infdis/jiq104
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发表时间:
2011-03-01
影响因子:
6.4
通讯作者:
Chotivanich, Kesinee
Chotivanich, Kesinee
中科院分区:
医学2区
文献类型:
--
作者:
Nantakomol, Duangdao;Dondorp, Arjen M.;Chotivanich, Kesinee

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在恶性疟疾患者中,细胞源性微粒的血浆浓度与疾病严重程度相关。利用流式细胞术,我们定量了疟疾患者的红细胞衍生微粒(RMPs),并确定了其来源和与产生相关的因素。恶性疟原虫(n = 29,中位数为457 RMPs/亩L[范围,13-4,342 RMPs/亩L])、间日疟原虫(n = 5,中位数为409 RMPs/亩L[范围,281-503/亩L])和疟疾疟原虫(n = 2,中位数为163 RMPs/亩L[范围,127-200 RMPs/亩L])患者的RMP浓度均高于健康受试者(n = 11,中位数为8 RMPs/亩L[范围,3-166 RMPs/亩L], P = 0.01)。重度恶性疟疾患者RMP浓度最高(P = 0.01)。被寄生的红细胞产生的RMPs比未被寄生的细胞多10倍,但总的来说,大多数RMPs仍然来自未感染的红细胞(URBCs)。在培养中,RMP产量随着寄生虫的成熟而增加。血红素和寄生虫产物诱导了RMP的产生,而RMP的产生被n -乙酰半胱氨酸抑制,这表明血红素介导的氧化应激是RMP产生的途径。
In patients with falciparum malaria, plasma concentrations of cell-derived microparticles correlate with disease severity. Using flow cytometry, we quantified red blood cell-derived microparticles (RMPs) in patients with malaria and identified the source and the factors associated with production. RMP concentrations were increased in patients with Plasmodium falciparum (n = 29; median, 457 RMPs/mu L [range, 13-4,342 RMPs/mu L]), Plasmodium vivax (n = 5; median, 409 RMPs/mu L [range, 281-503/mu L]), and Plasmodium malariae (n = 2; median, 163 RMPs/mu L [range, 127-200 RMPs/mu L]) compared with those in healthy subjects (n = 11; median, 8 RMPs/mu L [range, 3-166 RMPs/mu L]; P = .01). RMP concentrations were highest in patients with severe falciparum malaria (P = .01). Parasitized red cells produced > 10 times more RMPs than did unparasitized cells, but the overall majority of RMPs still derived from uninfected red blood cells (URBCs). In cultures, RMP production increased as the parasites matured. Hemin and parasite products induced RMP production in URBCs, which was inhibited by N-acetylcysteine, suggesting heme-mediated oxidative stress as a pathway for the generation of RMPs.