Accelerated senescence of human erythrocytes cultured with Plasmodium falciparum
Accelerated senescence of human erythrocytes cultured with Plasmodium falciparum
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DOI：
10.1182/blood-2002-08-2437
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发表时间：
2003-07-15
期刊：
影响因子：
20.3
通讯作者：
Taramelli, D
中科院分区：
文献类型：
--
作者：
Omodeo-Salè, F;Motti, A;Taramelli, D
感染恶性疟原虫 (IRBC) 的红细胞主要会发生细胞膜成分的变化，从而导致疟疾的发病机制。然而，所有的表现（例如贫血）不能仅由 IRBC 来解释。未感染的红细胞（URBC）可能发挥了一定作用，但对其的研究还不够充分。我们想要记录红细胞膜的变化，这些变化可能导致 URBC 寿命缩短和疟疾相关贫血。将人红细胞与恶性疟原虫一起培养，并在滋养体阶段进行洗涤。在Percoll密度梯度上分离IRBC和URBC，从而获得不同密度/年龄的红细胞分数。对 IRBC 和 URBC 纯化的膜进行分析，并与来自同一供体、保存在相同条件下的同龄对照正常红细胞 (NRBC) 进行比较。恶性疟原虫加速了 IRBC 和 URBC 的衰老，导致细胞群显着转向更密集（旧）的部分。 IRBC 和年轻 URBC 中的蛋白质、磷脂和胆固醇含量均降低。年轻和中等未感染的部分具有较高水平的脂质过氧化和磷脂饱和度（因为多不饱和脂肪酸，PUFA的损失）和较低的磷脂酰丝氨酸。在 IRBC 中，硫代巴比妥反应物质 (TBARS) 高于 NRBC 和 URBC，而 PUFA 和磷脂酰丝氨酸低于 NRBC 和 URBC。相比之下，滋养体膜的磷脂（特别是鞘磷脂和磷脂酰丝氨酸）和胆固醇含量较低，饱和度较高。寄生虫引起的过氧化损伤可能是这些改变的原因。总之，我们证明，导致感染和未感染红细胞加速衰老的膜损伤可能会导致疟疾贫血。 (C) 2003 年，美国血液学会。
Red blood cells Infected with Plasmodium falciparum (IRBCs) undergo changes primarily In their membrane composition that contribute to malaria pathogenesis. However, all manifestations (eg, anemia) cannot be accounted for by IRBCs alone. Uninfected erythrocytes (URBCs) may play a role, but they have been under-researched. We wanted to document changes In the erythrocyte membrane that could contribute to URBC reduced life span and malaria-associated anemia. Human erythrocytes were cultured with P falciparum and washed at the trophozoite stage. IRBCs and URBCs were separated on Percoll density gradient, thus obtaining erythrocyte fractions of different densities/ages. IRBC- and URBC-purified membranes were analyzed and compared with control normal erythrocytes (NRBCs) of the same age, from the same donor, kept In the same conditions. P falciparum accelerated aging of both IRBCs and URBCs, causing a significant shift In the cell population toward the denser (old) fraction. Protein, phospholipid, and cholesterol content were reduced In IRBCs and young URBCs. Young and medium uninfected fractions had higher levels of lipid peroxidation and phospholipid saturation (because of the loss of polyunsaturated fatty acids, PUFAs) and lower phosphatidylserine. In IRBCs, thiobarbituric reactive substances (TBARSs) were higher, and PUFAs and phosphatidylserine lower than In NRBCs and URBCs. In comparison, trophozoite membranes had lower phospholipid (particularly aphingomyelin and phosphatidylserine) and cholesterol content and a higher degree of saturation. Parasite-Induced peroxidative damage might account for these modifications. in summary, we demonstrated that membrane damage leading to accelerated senescence of both Infected and uninfected erythrocytes will likely contribute to malaria anemia. (C) 2003 by The American Society of Hematology.