title: Ring-infected erythrocyte surface antigen (Pf/155RESA) induces tumour necrosis factor-alpha production.
abstract: Cerebral malaria is probably related to an overstimulation of the immune system and the cytokine network. We have previously demonstrated that tumour necrosis factor (TNF) secretion by human macrophages can be induced by soluble and heat-stable malarial antigens. Indirect evidence from epidemiological and in vitro studies suggests that Pf155/RESA can be considered as a candidate for triggering TNF secretion. Thus we conducted experiments to investigate the relationship between Pf155/RESA and TNF production. The SGE1 strain of Plasmodium falciparum was compared with the P. falciparum FCR3 strain, which does not express Pf155/RESA protein, for ability to induce TNF secretion by normal human macrophages in vitro. Synthetic peptides from the Pf155/RESA antigen ((EENV)4, (EENVEHDA)4, (DDEHVEEPTVA)3), were used in some experiments. TNF levels were measured by an immunoradiometric assay. We observed that the RESA-defective strain induces lower levels of TNF after schizont rupture than the SGE1 strain. Moreover, substantial TNF secretion was detected when macrophages were incubated with all three peptides, maximum levels being obtained with the (EENV)4 peptide. Although previous reports have described TNF-inducing activity of phospholipid from P. falciparum, these findings strengthen the evidence for Pf155/RESA antigens also being involved in TNF production during malaria.
authors.affiliation: Département de Parasitologie-Mycologie Médicale et Moléculaire, Faculté de Médecine, Université Joseph Fourier, CNRS ERS-15, Grenoble, France.
authors.forename: S
authors.initials: S
authors.lastname: Picot
authors.forename: F
authors.initials: F
authors.lastname: Peyron
authors.forename: P
authors.initials: P
authors.lastname: Deloron
authors.forename: C
authors.initials: C
authors.lastname: Boudin
authors.forename: B
authors.initials: B
authors.lastname: Chumpitazi
authors.forename: G
authors.initials: G
authors.lastname: Barbe
authors.forename: J P
authors.initials: JP
authors.lastname: Vuillez
authors.forename: A
authors.initials: A
authors.lastname: Donadille
authors.forename: P
authors.initials: P
authors.lastname: Ambroise-Thomas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology; D000953:Antigens, Protozoan / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology*; D006801:Humans; D018950:Lipopolysaccharide Receptors; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000502:physiology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D018950:Lipopolysaccharide Receptors; D010446:Peptide Fragments; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum