A monoclonal antibody that recognizes phosphatidylinositol inhibits induction of tumor necrosis factor alpha by different strains of Plasmodium falciparum.
The clinical symptoms of human malaria are mediated, at least in part, by the release of tumor necrosis factor alpha (TNF) by monocytes and macrophages. We have found that lysates of Plasmodium falciparum-infected erythrocytes stimulate the secretion of TNF from human mononuclear cells, and we have generated several immunoglobulin M monoclonal antibodies (MAbs) that inhibit the induction of TNF by such lysates. Here we describe the properties of MAb 5AB3-11, which causes dose-dependent inhibition of the TNF-inducing factors derived from P. falciparum-infected erythrocytes, with a 50% reduction in TNF secretion at nanomolar concentrations (1 to 2 micrograms/ml). The inhibitory effect appears to be malaria specific in that the induction of TNF by either lipopolysaccharide or lipoteichoic acid is not affected. MAb 5AB3-11 binds to liposomes containing phosphatidylinositol but not to other phospholipid liposomes, showing that it recognizes a phosphatidylinositol-like epitope. MAb 5AB3-11 inhibits the induction of TNF by whole lysates from several strains of P. falciparum which originated from different parts of the tropics, indicating that all of the major TNF-inducing factors derived from Plasmodium-infected erythrocytes contain a common epitope. A phosphatidylinositol-like epitope expressed by Plasmodium-infected erythrocytes may be a suitable immunological target for the prevention or treatment of severe malaria.
Department of Paediatrics, John Radcliffe Hospital, Oxford, United Kingdom.
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Kwiatkowski
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000913:Antibodies, Protozoan / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008081:Liposomes / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010716:Phosphatidylinositols / Q000276:immunology*; D013045:Species Specificity; D013682:Teichoic Acids / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D008081:Liposomes; D010716:Phosphatidylinositols; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid