RING-INFECTED ERYTHROCYTE SURFACE-ANTIGEN (PF 155RESA) INDUCES TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION/

Cerebral malaria is probably related to an overstimulation of the immu ne system and the cytokine network. We have previously demonstrated th at tumour necrosis factor (TNF) secretion by human macrophages can be induced by soluble and heat-stable malarial antigens. Indirect evidenc e from epidemiological and in vitro studies suggests that Pf155/RESA c an be considered as a candidate for triggering TNF secretion. Thus we conducted experiments to investigate the relationship between Pf155/RE SA and TNF production. The SGE1 strain of Plasmodium falciparum was co mpared with the P. falciparum FCR3 strain, which does not express Pf15 5/RESA protein, for ability to induce TNF secretion by normal human ma crophages in vitro. Synthetic peptides from the Pf155/RESA antigen ((E ENV)4, (EENVEHDA)4, (DDEHVEEPTVA)3), were used in some experiments. TN F 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, maxi mum levels being obtained with the (EENV)4 peptide. Although previous reports have described TNF-inducing activity of phospholipid from P. f alciparum, these findings strengthen the evidence for Pf155/RESA antig ens also being involved in TNF production during malaria.