Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence.
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.
D D
DD
Roberts
J A
JA
Sherwood
S L
SL
Spitalnik
L J
LJ
Panton
R J
RJ
Howard
V M
VM
Dixit
W A
WA
Frazier
L H
LH
Miller
V
V
Ginsburg
D000818:Animals; D001029:Aotus trivirgatus; D002448:Cell Adhesion; D004727:Endothelium / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology*; D005169:Factor VIII / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008288:Malaria / Q000097:blood*; D008545:Melanoma / Q000378:metabolism; D010963:Plasmodium falciparum; D012995:Solubility; D019699:Thrombospondins; D019096:Vitronectin
D005353:Fibronectins; D006023:Glycoproteins; D007797:Laminin; D019699:Thrombospondins; D019096:Vitronectin; D005169:Factor VIII