The homeostasis of Plasmodium falciparum-infected red blood cells.
The homeostasis of Plasmodium falciparum-infected red blood cells.
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DOI：
10.1371/journal.pcbi.1000339
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发表时间：
2009-04
影响因子：
4.3
通讯作者：
Lew VL
中科院分区：
文献类型：
--
作者：
Mauritz JM;Esposito A;Ginsburg H;Kaminski CF;Tiffert T;Lew VL
恶性疟原虫是导致严重疟疾的寄生虫，其无性繁殖周期发生在红细胞内。裂殖子侵入循环中的红细胞，发育和繁殖，大约48小时后破坏宿主细胞，释放15-32个裂殖子，准备入侵新的红细胞。在这个周期中，寄生虫会极大地增加宿主细胞的通透性，以至于当在未感染的红细胞上模拟类似的通透性时，裂解发生在∼之前48小时。那么，在寄生虫完成其发育周期之前，感染的细胞如何在寄生虫完成发育周期之前阻止裂解？一个感染红细胞内稳态的数学模型表明，正是宿主细胞血红蛋白的浪费消耗，通过宿主体内胶体渗透压的逐渐降低(胶体渗透假说)阻止了早期的溶解。然而，两个关键的模型预测仍然存在争议，即感染的细胞将膨胀到接近裂解前的球状，以及血红蛋白浓度将逐渐降低。在这篇文章中，我们第一次能够将模型预测与文献中最近的实验数据相关联，并探索在寄生虫发展的五个模型定义的时期中感染的红细胞的动态平衡的细节。这些结论表明，感染的红细胞无论其实际体积如何，都会接近溶解破裂，因此需要逐步降低其血红蛋白浓度，以防止过早溶解。恶性疟原虫是人类严重疟疾的罪魁祸首。寄生虫在红细胞内的48小时无性繁殖周期是导致这种疾病症状的原因。在这段时间内，寄生虫会引起宿主红细胞的巨大变化，使一些代谢活动增加百倍，使其泄漏到许多营养物质和废物中，并消耗细胞的大部分血红蛋白，远远超过其自身新陈代谢所需。我们面临的挑战是解释受感染的细胞如何在如此激烈的循环中保持其完整性。为了寻找线索，我们开发了一个感染细胞的数学模型，在这个模型中，我们编码了我们目前对控制细胞内稳态的复杂过程的知识和理解。我们在这里首次详细描述了该模型，并根据现有的实验证据对其预测进行了批判性分析。这些结果支持这样的观点，即宿主细胞内的血红蛋白浓度逐渐降低，导致肿胀的速度和程度降低，从而维持宿主细胞的完整性。
The asexual reproduction cycle of Plasmodium falciparum, the parasite responsible for severe malaria, occurs within red blood cells. A merozoite invades a red cell in the circulation, develops and multiplies, and after about 48 hours ruptures the host cell, releasing 15–32 merozoites ready to invade new red blood cells. During this cycle, the parasite increases the host cell permeability so much that when similar permeabilization was simulated on uninfected red cells, lysis occurred before ∼48 h. So how could infected cells, with a growing parasite inside, prevent lysis before the parasite has completed its developmental cycle? A mathematical model of the homeostasis of infected red cells suggested that it is the wasteful consumption of host cell hemoglobin that prevents early lysis by the progressive reduction in the colloid-osmotic pressure within the host (the colloid-osmotic hypothesis). However, two critical model predictions, that infected cells would swell to near prelytic sphericity and that the hemoglobin concentration would become progressively reduced, remained controversial. In this paper, we are able for the first time to correlate model predictions with recent experimental data in the literature and explore the fine details of the homeostasis of infected red blood cells during five model-defined periods of parasite development. The conclusions suggest that infected red cells do reach proximity to lytic rupture regardless of their actual volume, thus requiring a progressive reduction in their hemoglobin concentration to prevent premature lysis. The parasite Plasmodium falciparum is responsible for severe malaria in humans. The 48 hour asexual reproduction cycle of the parasite within red blood cells is responsible for the symptoms in this disease. Within this period, the parasite causes massive changes in the host red cell, increasing some metabolic activities hundredfold, making it leaky to many nutrients and waste products, and consuming most of the cell's hemoglobin, far more than it needs for its own metabolism. The challenge that we faced was to explain how the infected cell maintained its integrity throughout such a violent cycle. Seeking clues, we developed a mathematical model of an infected cell in which we encoded our current knowledge and understanding of the complex processes that control cell homeostasis. We present here for the first time a detailed description of the model and a critical analysis of its predictions in relation to the available experimental evidence. The results support the view that host-cell integrity is maintained by the progressive reduction in the hemoglobin concentration within the host cell, resulting in a reduced rate and extent of swelling.
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影响因子：
9.6
作者：
Allen, RJW;Kirk, K
通讯作者：
Kirk, K
DOI：
10.1111/j.1749-6632.1974.tb19108.x
发表时间：
1974-01-01
影响因子：
5.2
作者：
GARRAHAN, PJ;GARAY, RP
通讯作者：
GARAY, RP
DOI：
10.1073/pnas.0711067105
发表时间：
2008-02-19
影响因子：
11.1
作者：
Elliott, David A.;McIntosh, Michael T.;Joiner, Keith A.
通讯作者：
Joiner, Keith A.
影响因子：
3.7
作者：
Esposito A;Tiffert T;Mauritz JM;Schlachter S;Bannister LH;Kaminski CF;Lew VL
通讯作者：
Lew VL
影响因子：
4.1
作者：
Elliott, JL;Saliba, KJ;Kirk, K
通讯作者：
Kirk, K