Plasmodium falciparum erythrocyte rosetting is mediated by promiscuous lectin-like interactions

doi:10.1084/jem.176.5.1311

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Plasmodium falciparum erythrocyte rosetting is mediated by promiscuous lectin-like interactions

J Carlson and M Wahlgren
Department of Immunology, Stockholm University, Sweden.

Herein we describe an assay that was developed to quantitate the binding of normal red blood cells (RBC), labeled with carboxy fluorescein diacetate (C-FDA), to rosetting Plasmodium falciparum- infected RBC. The binding of RBC obtained from various animal species or humans to different strains or clones of rosetting P. falciparum- infected RBC was studied. A strain-specific preference of rosetting was observed for either blood group A/AB or B/AB RBC for all parasites tested. The higher affinity of rosette binding of blood group A, B, or AB vs. O RBC was reflected in larger rosettes when a given parasite was grown in RBC of the preferred blood group. The small size of the rosettes formed when P. falciparum was grown in blood group O RBC may be the in vitro correlate of the relative protection against cerebral malaria afforded by belonging to blood group O rather than to blood group A or B. Rosettes of a blood group A-preferring parasite could be completely disrupted by heparin only when grown in blood group O or B RBC, but not when grown in blood group A RBC. Similarly, the rosettes of a blood group B-preferring parasite could be more easily disrupted by heparin when grown in blood group O or A RBC than when grown in blood group B RBC. Several different saccharides inhibited rosetting of group O RBC, including two monosaccharides that are basic components of heparin. The rosetting of the same parasites grown in blood group A or B RBC was less sensitive to heparin and was specifically inhibited only by the terminal mono- and trisaccharides of the A and the B blood group antigens, the H disaccharide, and fucose. Our results suggest that rosetting is mediated by multiple lectin-like interactions, the usage of which rely on the parasite phenotype and whether the receptors are present on the host cell or not.
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