Plasmodium falciparum-infected erythrocytes do not adhere well to C32 melanoma cells or CD36 unless rosettes with uninfected erythrocytes are first disrupted.
Plasmodium falciparum malaria parasites modify the human erythrocytes in which they grow so that some parasitized erythrocytes (PE) can cytoadhere (C+) to host vascular endothelial cells or adhere in rosettes (R+) to uninfected erythrocytes. These C+ and R+ adherence properties of PE appear to mediate much of the pathogenesis of severe malaria infections, in part by blocking blood flow in microvessels. From one parasite strain, PE were selected in vitro for C+ R+ or C+ R- adherence properties and examined in model adherence assays. The C+ R+ PE cytoadhered poorly to C32 melanoma cells or to immobilized CD36 in a settled-cell assay when uninfected human erythrocytes were present and formed rosettes with PE. C+ R- PE adhered well in the same assays. However, C+ R+ PE adhered very well, even better than C+ R- PE, when the rosettes were disrupted and the C+ R+ PE were purified. Adding back rabbit erythrocytes, which do not form rosettes with C+ R+ PE, had simply a dilutional effect. The ability of rosettes to interfere with the detection of adherence must be dealt with in all future assays of malarial PE adherence. Individual PE were observed attached simultaneously to C32 cells and to a few erythrocytes, suggesting that C+ and R+ adherence properties are coexpressed on the same PE. Coexpression of these adherence properties on the same PE may have pathological importance in vivo, where passage of rosettes through capillaries may shear uninfected erythrocytes from rosetted PE and allow direct PE attachment to postcapillary venule walls before rosettes reform.
Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304-1104.
S M
SM
Handunnetti
T H
TH
Hasler
R J
RJ
Howard
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D018955:CD36 Antigens; D002448:Cell Adhesion; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D006801:Humans; D008546:Melanoma, Experimental / Q000473:pathology*; D010963:Plasmodium falciparum / Q000502:physiology*; D011817:Rabbits; D012397:Rosette Formation
D015703:Antigens, CD; D018955:CD36 Antigens