A Plasmodium falciparum isolate with a chromosome 9 deletion expresses a trypsin-resistant cytoadherence molecule.
Sequestration of Plasmodium falciparum infected erythrocytes in the cerebral circulation is strongly implicated in the pathogenesis of cerebral malaria. From previous studies it was postulated that genes essential for cytoadherence were located on the right arm of chromosome 9 as P. falciparum isolates with a deletion in this region lost the capacity to cytoadhere in vitro and no longer expressed Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) on the surface of the infected cells. We have selected a P. falciparum isolate from Papua New Guinea for high levels of cytoadherence to human umbilical vein endothelial cells (HUVECs) and have shown that the cloned parasite has several novel properties related to cytoadherence. The cloned parasite adheres to HUVECs, does not bind to melanoma cells, and expresses a surface molecule with most of the properties of PfEMP-1, despite a deletion in the right arm of chromosome 9. Interestingly, the surface expressed PfEMP-1 in this strain is resistant to trypsin treatment and infected cells continue to cytoadhere after trypsin digestion at a concentration of 100 micrograms ml-1. The receptor on HUVECs for the cloned parasite lines is a molecule different from any previously described, as parasitized cells do not adhere to soluble intercellular adhesion molecule 1, thrombospondin, vascular cell adhesion molecule 1, E-selectin or P-selectin, nor to CD36. Our work, taken together with the results from previous studies, suggest that the ability of parasites to cytoadhere is encoded in at least two distinct genomic locations in the parasite, and the diversity of receptor-ligand interaction is greater than previously described.
Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria, Australia.
S C
SC
Chaiyaroj
R L
RL
Coppel
C
C
Magowan
G V
GV
Brown
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002460:Cell Line; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology; D017125:Genes, Protozoan; D006801:Humans; D008288:Malaria / Q000209:etiology; D010641:Phenotype; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics; D014162:Transfection; D014357:Trypsin / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D015800:Protozoan Proteins; D014357:Trypsin