Hemolytic anemia is one of the hallmarks of malaria and leads to an increase in oxidized heme (hemin) within the plasma of infected individuals. While scavenger proteins sequester much of the circulating heme, it has been hypothesized that extracellular heme may play a central role in malaria pathogenesis. We have previously developed the multiplex fluidic plunger (MFP) device for the measurement of red blood cell (RBC) deformability. Here, we demonstrate that the measurement of changes in RBC deformability is a sensitive method for inferring heme-induced oxidative stress. We further show that extracellular hemin concentration correlates closely with changes in RBC deformability and we confirm that this biophysical change correlates with other indicators of cell stress. Finally, we show that reduced erythrocyte deformability corresponds with both erythrophagocytosis and RBC osmotic fragility. The MFP microfluidic device presents a simple and potentially inexpensive alternative to existing methods for measuring hemolytic cell stress that could ultimately be used to perform clinical assessment of disease progression in severe malaria.

中文翻译：

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红细胞变形性的微流分析，作为评估由恶性疟原虫红细胞内寄生虫引起的血红素诱导的氧化应激的一种手段。

溶血性贫血是疟疾的标志之一，并导致感染个体血浆中氧化血红素（血红素）的增加。尽管清除剂蛋白螯合了大部分循环血红素，但据推测，细胞外血红素可能在疟疾发病机理中发挥重要作用。我们先前已经开发出用于测量红细胞（RBC）变形能力的多路流体柱塞（MFP）设备。在这里，我们证明RBC变形能力的变化的测量是一种推断血红素诱导的氧化应激的灵敏方法。我们进一步表明，细胞外血红素浓度与RBC变形能力的变化密切相关，并且我们确认该生物物理变化与细胞应激的其他指标相关。最后，我们表明减少的红细胞变形能力与红细胞吞噬作用和RBC渗透脆性相对应。MFP微流控设备提供了一种简单且可能便宜的替代方法，可替代现有的用于测量溶血性细胞应激的方法，该方法最终可用于对严重疟疾进行疾病进展的临床评估。