title: Antimalarial drugs inhibit the phagocytosis of erythrocytes infected with Plasmodium falciparum.
abstract: Phagocytic cells constitute the first line of defence against malarial parasites. They perform their role by delivering oxidative radicals and by phagocytosing infected red blood cells (IRBC). Phagocytosis is mediated by antibody binding to clustered band 3 antigen in the IRBC membrane and activation of the alternative complement pathway. In this study we showed that treatment of IRBC containing Plasmodium falciparum with therapeutically-relevant concentrations of antimalarial drugs considerably reduced the binding of immunoglobulin G (IgG) to, and the phagocytosis of, IRBC. Opsonization of IRBC by fresh serum before drug treatment prevented this inhibitory action of drugs. Removal of the drug restored IgG binding and the phagocytic susceptibility of IRBC in a time-dependent fashion. Direct measurement of the effect of chloroquine on the clustering of band 3 in IRBC, however, failed to reveal any disruption of the aggregation. We conclude that antimalarial drugs are able to alter, by an as yet unresolved mechanism, the affinity of IgG to clustered band 3. This affinity of IRBC seems to be determined by a dynamic process that depends on the metabolic activity of the parasite.
authors.affiliation: Department of Biological Chemistry, Hebrew University, Jerusalem, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Shalmiev
authors.forename: M
authors.initials: M
authors.lastname: Krugliak
authors.forename: F
authors.initials: F
authors.lastname: Turrini
authors.forename: H
authors.initials: H
authors.lastname: Ginsburg
mesh_terms: D000915:Antibody Affinity / Q000187:drug effects; D000962:Antimalarials / Q000494:pharmacology*; D001323:Autoantibodies / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D006801:Humans; D007074:Immunoglobulin G; D066298:In Vitro Techniques; D016778:Malaria, Falciparum / Q000188:drug therapy*; D009000:Monocytes / Q000187:drug effects; D009895:Opsonin Proteins; D010587:Phagocytosis / Q000187:drug effects; D013997:Time Factors
chemical_list: D000962:Antimalarials; D001323:Autoantibodies; D007074:Immunoglobulin G; D009895:Opsonin Proteins