title: Antibodies to a histidine-rich protein (PfHRP1) disrupt spontaneously formed Plasmodium falciparum erythrocyte rosettes.
abstract: Cerebral involvement in Plasmodium falciparum malaria is associated with sequestration of infected red blood cells and occlusion of cerebral vessels. Adhesion of infected erythrocytes along the vascular endothelium as well as binding of uninfected erythrocytes to cells infected with late-stage asexual parasites (rosetting) may be important in erythrocyte sequestration. We report that the recently discovered rosetting phenomenon shares characteristics with other human cell-cell interactions (heparin sensitivity, temperature independence, Ca2+/Mg2+ and pH dependence). Mono- and polyclonal antibodies specific for PfHRP1, a histidine-rich protein present in the membrane of P. falciparum-infected erythrocytes, disrupt rosettes but do not affect attachment of infected erythrocytes to endothelial cells. The inhibitory anti-PfHRP1 antibodies reacted with rosetting parasites in indirect immunofluorescence and with P. falciparum polypeptides of Mr 28,000 and Mr 90,000 in immunoprecipitation and immunoblotting, respectively. No inhibitory effects on erythrocyte rosetting were obtained with antibodies to related histidine-rich or other antigens of P. lophurae or P. falciparum. Whether the epitope that mediates rosetting, and is recognized by the anti-PfHRP1 antibodies, is located on PfHRP1 or on a crossreactive antigen remains to be established. The results suggest that endothelial cytoadherence and erythrocyte rosetting involve different molecular mechanisms.
authors.affiliation: Department of Immunology, University of Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Carlson
authors.forename: G
authors.initials: G
authors.lastname: Holmquist
authors.forename: D W
authors.initials: DW
authors.lastname: Taylor
authors.forename: P
authors.initials: P
authors.lastname: Perlmann
authors.forename: M
authors.initials: M
authors.lastname: Wahlgren
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D004492:Edetic Acid / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology*; D005455:Fluorescent Antibody Technique; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D010963:Plasmodium falciparum / Q000187:drug effects / Q000502:physiology*; D011506:Proteins / Q000276:immunology / Q000502:physiology*; D015800:Protozoan Proteins; D012397:Rosette Formation; D013696:Temperature; D000099053:Histidine-Rich Glycoprotein
chemical_list: D000911:Antibodies, Monoclonal; D002951:Citrates; D011506:Proteins; D015800:Protozoan Proteins; D000099053:Histidine-Rich Glycoprotein; D019343:Citric Acid; D006493:Heparin; D004492:Edetic Acid