Competitive endothelial adhesion between Plasmodium falciparum isolates under physiological flow conditions.
BACKGROUND
Sequestration of parasitized red blood cells in the microvasculature of major organs involves a sequence of events that is believed to contribute to the pathogenesis of severe falciparum malaria. Plasmodium falciparum infections are commonly composed of multiple subpopulations of parasites with varied adhesive properties. A key question is: do these subpopulations compete for adhesion to endothelium? This study investigated whether, in a laboratory model of cytoadherence, there is competition in binding to endothelium between pRBC infected with P. falciparum of variant adhesive phenotypes, particularly under flow conditions.


METHODS
Four different P. falciparum isolates, of known adherence phenotypes, were matched in pairs, mixed in different proportions and allowed to bind to cultured human endothelium. Using in vitro competitive static and flow-based adhesion assays, that allow simultaneous testing of the adhesive properties of two different parasite lines, adherence levels of paired P. falciparum isolates were quantified and analysed using either non-parametric Wilcoxon's paired signed rank test or Student paired test.


RESULTS
Study findings show that P. falciparum parasite lines show marked differences in the efficiency of adhesion to endothelium.


CONCLUSIONS
Plasmodium falciparum variants will compete for adhesion to endothelia and variants can be ranked by their efficiency of binding. These findings suggest that variants from a mixed infection will not show uniform cytoadherence and so may vary in their ability to cause disease.
Phiri
Happy
H
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Chichiri, Blantyre 3, Malawi. hphiri@mlw.medcol.mw
Montgomery
Jacqui
J
Molyneux
Malcolm
M
Craig
Alister
A
D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000469:parasitology*; D006801:Humans; D066298:In Vitro Techniques; D010641:Phenotype; D010963:Plasmodium falciparum / Q000502:physiology*; D018709:Statistics, Nonparametric