THROMBOSPONDIN BINDS FALCIPARUM-MALARIA PARASITIZED ERYTHROCYTES AND MAY MEDIATE CYTOADHERENCE
THROMBOSPONDIN BINDS FALCIPARUM-MALARIA PARASITIZED ERYTHROCYTES AND MAY MEDIATE CYTOADHERENCE
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DOI：
10.1038/318064a0
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发表时间：
1985-01-01
期刊：
影响因子：
64.8
通讯作者：
GINSBURG, V
中科院分区：
文献类型：
--
作者：
ROBERTS, DD;SHERWOOD, JA;GINSBURG, V
恶性疟原虫感染的红细胞含有成熟滋养体和裂殖体，沿静脉内皮细胞隔离，不在疟疾患者的外周循环中。旋钮出现在受感染的红细胞上，是内皮细胞的附着点。隔离可能保护寄生虫免受脾的破坏，并可能在脑型疟疾的发病机制中发挥作用。利用培养的人内皮细胞和一种无色素性黑色素瘤细胞系，已经在体外开发了隔离的相关性。恶性疟原虫无核株(K-)在体内不能隔离，在体外不能与细胞结合。我们现在提出的证据表明，细胞黏附的受体是糖蛋白，即凝血酶原蛋白。含有结节(K+)的Aotus猴或人红细胞与固定化的凝血酶原蛋白结合，而含有无结节恶性疟原虫株的Aotus红细胞不结合。这两种蛋白都不能与层粘连蛋白、纤维连接蛋白、第VIII因子/血管性血友病因子或玻璃体结合蛋白结合。可溶性血栓反应蛋白和抗血栓反应蛋白抗体均可抑制寄生的Aotus红细胞与凝血酶反应蛋白的结合，以及与分泌血栓反应蛋白的黑色素瘤细胞的结合。
Plasmodium falciparum infected erythrocytes containing mature trophozoites and schizonts sequester along venular endothelium and are not in the peripheral circulation of patients with malaria. Knobs appear on infected erythrocytes and are the points of attachment to endothelium. Sequestration may protect the parasite from splenic destruction and may play a role in the pathogenesis of cerebral malaria. Correlates of sequestration have been developed in vitro using cultured human endothelium and an amelanotic melanoma cell line. Knobless strains (K-) of P. falciparum fail to sequester in vivo and to bind to cells in vitro. We now present evidence that the receptor for cytoadherence is the glycoprotein, thrombospondin. Aotus monkey or human erythrocytes containing knobby (K+) but not Aotus erythrocytes containing knobless strains of P. falciparum bind to immobilized thrombospondin. Neither binds to the adhesive proteins laminin, fibronectin, factor VIII/von Willebrand factor or vitronectin. Both soluble thrombospondin and anti-thrombospondin antibodies inhibit binding of parasitized Aotus erythrocytes to immobilize thrombospondin and to melanoma cells which secrete thrombospondin.