Plasmodium falciparum uses gC1qR/HABP1/p32 as a receptor to bind to vascular endothelium and for platelet-mediated clumping.
Plasmodium falciparum uses gC1qR/HABP1/p32 as a receptor to bind to vascular endothelium and for platelet-mediated clumping.
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DOI：
10.1371/journal.ppat.0030130
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发表时间：
2007-09-07
期刊：
影响因子：
6.7
通讯作者：
Chitnis CE
中科院分区：
文献类型：
--
作者：
Biswas AK;Hafiz A;Banerjee B;Kim KS;Datta K;Chitnis CE
恶性疟原虫感染的红细胞(IRBCs)与血管内皮细胞结合，从而能够隔离重要宿主器官的能力，是疟疾的重要致病机制。恶性疟原虫血红细胞与血小板的黏附导致红细胞聚集，是另一种与严重疾病相关的细胞黏附现象。在这里，我们使用体外细胞黏附试验首次证明，据我们所知，恶性疟原虫IRBCs使用32 kDa的人蛋白gC1qR/HABP1/p32作为受体与人脑微血管内皮细胞结合。此外，我们还发现恶性疟原虫IRBCs还可以与血小板上的gC1qR/HABP1/p32结合形成簇状。因此，我们的研究确定了一种新的宿主受体，它既可用于黏附血管内皮细胞，也可用于血小板介导的聚集。考虑到与血管内皮的黏附和血小板介导的聚集与严重疾病的相关性，恶性疟原虫IRBCs与gC1qR/HABP1/p32的黏附可能在疟疾的发病机制中发挥重要作用。恶性疟原虫感染的红细胞(IRBCs)与重要宿主器官毛细血管内皮细胞的黏附可阻碍血液循环，是疟疾的重要致病机制。恶性疟原虫血红细胞与血小板的黏附会导致红细胞聚集，这也会阻碍血液流动，并与严重疟疾有关。在这里，我们已经确定了一种新的细胞黏附受体，它同时存在于内皮细胞和血小板上。我们首次证明，据我们所知，恶性疟原虫IRBCs使用32 kDa的人类蛋白gC1qR/HABP1/p32作为受体与包括脑微血管内皮细胞在内的人内皮细胞结合。此外，我们还发现恶性疟原虫IRBCs可以与血小板上的gC1qR/HABP1/p32结合形成簇状。因此，我们的研究确定了一种新的宿主受体，它既可用于黏附血管内皮细胞，也可用于血小板介导的聚集。鉴于这些细胞黏附现象与严重疾病的关联，我们的研究为研究恶性疟原虫IRBCs与gC1qR/HABP1/p32黏附在疟疾发病机制中的作用打开了大门。
The ability of Plasmodium falciparum–infected red blood cells (IRBCs) to bind to vascular endothelium, thus enabling sequestration in vital host organs, is an important pathogenic mechanism in malaria. Adhesion of P. falciparum IRBCs to platelets, which results in the formation of IRBC clumps, is another cytoadherence phenomenon that is associated with severe disease. Here, we have used in vitro cytoadherence assays to demonstrate, to our knowledge for the first time, that P. falciparum IRBCs use the 32-kDa human protein gC1qR/HABP1/p32 as a receptor to bind to human brain microvascular endothelial cells. In addition, we show that P. falciparum IRBCs can also bind to gC1qR/HABP1/p32 on platelets to form clumps. Our study has thus identified a novel host receptor that is used for both adhesion to vascular endothelium and platelet-mediated clumping. Given the association of adhesion to vascular endothelium and platelet-mediated clumping with severe disease, adhesion to gC1qR/HABP1/p32 by P. falciparum IRBCs may play an important role in malaria pathogenesis. Adhesion of Plasmodium falciparum–infected red blood cells (IRBCs) to the endothelium lining the capillaries of vital host organs can obstruct blood circulation and is an important pathogenic mechanism in malaria. Adhesion of P. falciparum IRBCs to platelets results in the formation of IRBC clumps that can also obstruct blood flow and is implicated in severe malaria. Here, we have identified a novel cytoadherence receptor that is found on both endothelial cells and platelets. We demonstrate, for the first time to our knowledge, that P. falciparum IRBCs use the 32-kDa human protein gC1qR/HABP1/p32 as a receptor to bind to human endothelial cells, including brain microvascular endothelial cells. In addition, we show that P. falciparum IRBCs can bind to gC1qR/HABP1/p32 on platelets to form clumps. Our study has thus identified a novel host receptor that is used for both adhesion to vascular endothelium and platelet-mediated clumping. Given the association of these cytoadherence phenomena with severe disease, our study opens the door to investigations on the role of adhesion of P. falciparum IRBCs to gC1qR/HABP1/p32 in malaria pathogenesis.
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