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首页> 外文期刊>British Journal of Haematology >Transfer of 4-hydroxynonenal from parasitized to non-parasitized erythrocytes in rosettes. Proposed role in severe malaria anemia
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Transfer of 4-hydroxynonenal from parasitized to non-parasitized erythrocytes in rosettes. Proposed role in severe malaria anemia

机译：花环中4-羟基壬烯醛从寄生的红细胞转移到未寄生的红细胞。在严重疟疾贫血中的拟议作用

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摘要

Severe anaemia is a life-threatening complication of falciparum malaria associated with loss of predominantly non-parasitized red blood cells (npRBCs). This poorly elucidated process might be influenced by (i) rosettes, i.e. npRBCs cytoadherent to haemozoin-containing parasitized RBCs (pRBCs) and (ii) generation in pRBCs of 4-hydroxynonenal (4-HNE) through haemozoin-catalysed lipid peroxidation. We explored whether close proximity in rosettes may facilitate 4-HNE transfer to npRBCs, which is likely to enhance their phagocytosis and contribute to malaria anaemia. Fluorescence microscopy and flow cytometry data indicated 4-HNE transfer to npRBCs in rosettes. Rosettes were formed by 64·8±1·8% varO-expressing pRBCs, and 8·7±1·1% npRBCs were positive for 4-HNE-protein-conjugates, while low-rosetting parasites generated only 2·4±1·1% 4-HNE-conjugate-positive npRBCs. 4-HNE transfer decreased after blocking rosetting by monoclonal antibodies. A positive linear relationship between rosette frequency and 4-HNE-conjugates in npRBCs was found in 40 malaria patients, a first indication for a role of rosetting in npRBCs modifications in vivo. Children with severe malaria anaemia had significantly higher percentages of 4-HNE-conjugate-positive npRBCs compared to children with uncomplicated malaria. In conclusion, 4-HNE transfer from pRBCs to npRBCs in rosettes is suggested to play a role in the phagocytic removal of large numbers of npRBCs, the hallmark of severe malaria anaemia.
机译：严重贫血是致命的恶性疟疾并发症，主要与非寄生性红细胞（npRBC）丢失有关。这种难以阐明的过程可能受到以下因素的影响：（i）莲座丛，即与含血红素的寄生虫RBC（pRBCs）细胞粘附的npRBC，以及（ii）通过血红素催化的脂质过氧化作用在pRBC中生成4-羟基壬烯醛（4-HNE）。我们探讨了莲座丛中的近距离是否可能促进4-HNE向npRBC的转移，这可能会增强它们的吞噬作用并导致疟疾贫血。荧光显微镜和流式细胞术数据表明4-HNE转移到玫瑰花结中的npRBCs。玫瑰花结由表达varO的pRBCs形成64·8±1·8％，4-HNE-蛋白结合物呈阳性，有8·7±1·1％npRBCs呈阳性，而低速生长的寄生虫仅产生2·4±1。 ·1％的4-HNE共轭阳性npRBC。单克隆抗体阻断玫瑰花结后，4-HNE转移减少。在40位疟疾患者中，npRBC中的花环频率与4-HNE-缀合物之间存在正线性关系，这首次表明了花环在体内npRBCs修饰中的作用。与没有疟疾的儿童相比，患有严重疟疾的儿童的4-HNE-缀合物阳性npRBC的百分比明显更高。总之，建议在莲座丛中从pRBCs到npRBCs的4-HNE转移在吞噬去除大量npRBCs中发挥作用，这是严重疟疾贫血的标志。

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