Contribution of parasite proteins to altered mechanical properties of malaria-infected red blood cells

Contribution of parasite proteins to altered mechanical properties of malaria-infected red blood cells
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DOI:
10.1182/blood.v99.3.1060
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发表时间:
2002-02-01
期刊:
影响因子:
20.3
通讯作者:
Cooke, BM
Cooke, BM
中科院分区:
医学1区
文献类型:
--
作者:
Glenister, FK;Coppel, RL;Cooke, BM

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恶性疟原虫寄生的红细胞(RBC)僵硬,变形能力差,表现出异常的循环行为。在寄生虫发育过程中,结节相关富含组氨酸蛋白(Kahrp)和恶性疟原虫红细胞膜蛋白3(PfEMP3)从寄生虫中排出并与红细胞膜骨架相互作用。利用微管吸入法,测定了转基因寄生虫(缺失kahrp或pfemp3基因)感染的红细胞的膜剪切弹性模数,以确定这些蛋白对寄生红细胞(PRBC)刚性增加的贡献。在没有这两种蛋白的情况下,细胞膜的强直化程度明显低于正常亲本寄生虫克隆引起的水平。Kahrp对强直化的影响明显大于PfEMP3,对PRBC总增加的贡献率约为51%,而PfEMP3为15%。这项研究首次提供了关于特定寄生虫蛋白对PRBC机械性能改变的贡献的定量信息。(C)2002年,由美国血液病学会公布。
Red blood cells (RBCs) parasitized by Plasmodium falciparum are rigid and poorly deformable and show abnormal circulatory behavior. During parasite development, knob-associated histidine-rich protein (KAHRP) and P falciparum erythrocyte membrane protein 3(PfEMP3) are exported from the parasite and interact with the RBC membrane skeleton. Using micropipette aspiration, the membrane shear elastic modulus of RBCs infected with transgenic parasites (with kahrp or pfemp3 genes deleted) was measured to determine the contribution of these proteins to the increased rigidity of parasitized RBCs (PRBCs). In the absence of either protein, the level of membrane rigidification was significantly less than that caused by the normal parental parasite clone. KAHRP had a significantly greater effect on rigidification than PfEMP3, contributing approximately 51% of the overall Increase that occurs In PRBCs compared to 15% for PfEMP3. This study provides the first quantitative information on the contribution of specific parasite proteins to altered mechanical properties of PRBCs. (C) 2002 by The American Society of Hematology.