Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence

• Published in: Nature (London) 1985-11, Vol.318 (6041), p.64-66
• Main Authors: Roberts, David D, Sherwood, James A, Spitalnik, Steven L, Panton, Lindsey J, Howard, Russell J, Dixit, Vishva M, Frazier, William A, Miller, Louis H, Ginsburg, Victor
• Format: Article
• Language: English
• Subjects: Animals; Aotus trivirgatus; Biological and medical sciences; Cell Adhesion; Endothelium - metabolism; Erythrocytes - parasitology; Factor VIII - metabolism; Fibronectins - metabolism; Fundamental and applied biological sciences. Psychology; Glycoproteins - metabolism; Human protozoal diseases; Humanities and Social Sciences; Humans; Infectious diseases; Laminin - metabolism; letter; Life cycle. Host-agent relationship. Pathogenesis; Malaria; Malaria - blood; Medical sciences; Melanoma - metabolism; multidisciplinary; Parasitic diseases; Plasmodium falciparum; Protozoa; Protozoal diseases; Science; Science (multidisciplinary); Solubility; Thrombospondins; Tropical medicine; Vitronectin
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/318064a0

Plasmodium falciparum infected erythrocytes containing mature trophozoites and schizonts sequester along venular endothelium 1 and are not in the peripheral circulation of patients with malaria. Knobs appear on infected erythrocytes and are the points of attachment to endothelium 2 . Sequestration may protect the parasite from splenic destruction 3 and may play a role in the pathogenesis of cerebral malaria 4 . Correlates of sequestration have been developed in vitro using cultured human endothelium 5 and an amelanotic melanoma cell line 6 . 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 Wi lie brand 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.