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Tumor necrosis factor enhances eosinophil toxicity to Schistosoma mansoni larvae
Abstract:
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.
Insights
Tumor necrosis factor (TNF) enhances eosinophil toxicity against Schistosoma mansoni parasites, demonstrating an important immune regulatory role. This finding is crucial for clinical applications of TNF.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Tumor necrosis factor (TNF) is a monocyte-derived cytokine with known cytotoxic effects on tumor cells.
- Eosinophil-cytotoxicity-enhancing factor (M-ECEF) activates human eosinophils against Schistosoma mansoni larvae.
- The similarity in source and characteristics between TNF and M-ECEF suggested a potential functional link.
Purpose of the Study:
- To investigate whether Tumor necrosis factor (TNF) enhances eosinophil-mediated toxicity against Schistosoma mansoni.
- To determine if TNF shares functional or physical similarities with M-ECEF.
Main Methods:
- Recombinant human TNF was used to treat human eosinophils and neutrophils.
- Eosinophil and neutrophil toxicity against Schistosoma mansoni larvae was assessed.
- Co-elution of TNF and M-ECEF activity was analyzed using reversed-phase HPLC.
- Immunological identity was tested using anti-TNF antibody and protein A-Sepharose.
Main Results:
- TNF enhanced eosinophil toxicity to Schistosoma mansoni larvae in a dose-dependent manner.
- This enhancement was specific to eosinophils, with no effect observed on neutrophils.
- TNF and M-ECEF activity co-eluted during HPLC, indicating physical similarity.
- M-ECEF activity was reduced by anti-TNF antibody, suggesting partial immunological identity.
Conclusions:
- Tumor necrosis factor (TNF) enhances eosinophil function, specifically their toxicity to Schistosoma mansoni.
- TNF may represent a significant immunological regulatory mechanism.
- The findings highlight the importance of considering TNF's effect on eosinophils in clinical settings.