Tumor necrosis factor enhances eosinophil toxicity to Schistosoma mansoni larvae.
Tumor necrosis factor (TNF) is a monocyte product that kills or inhibits the growth of certain tumor cells. Its cell source and physical characteristics suggest that it is similar to a monokine, eosinophil-cytotoxicity-enhancing factor (M-ECEF), that activates human eosinophil toxicity to Schistosoma mansoni larvae. The availability of recombinant human TNF allowed us to test this possibility. The data show that TNF has no direct effect on the parasites but enhances eosinophil toxicity to the parasites in a dose-dependent fashion. This effect is specific for eosinophils and not neutrophils. TNF and the eosinophil-specific activity of TNF are coeluted with M-ECEF in reversed-phase HPLC. Further, M-ECEF activity in HPLC fractions is reduced by treatment with rabbit anti-TNF antibody and protein A-Sepharose. This demonstrates physical similarity and at least partial immunological identity of TNF and a fraction of M-ECEF. Thus, TNF can enhance eosinophil function and may constitute an important immunological regulatory mechanism. This effect should be considered when TNF is applied clinically.
Silberstein
D S
DS
David
J R
JR
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D006023:Glycoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007814:Larva; D008222:Lymphokines / Q000302:isolation & purification / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology*; D012685:Sepharose / Q000031:analogs & derivatives; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha; D013205:Staphylococcal Protein A
D006023:Glycoproteins; D008222:Lymphokines; D011506:Proteins; D011994:Recombinant Proteins; D012685:Sepharose; D014409:Tumor Necrosis Factor-alpha; C042030:Staphylococcal protein A-sepharose; D013205:Staphylococcal Protein A; C022227:eosinophil stimulating promoter