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Tumor necrosis factor-alpha induction by reovirus serotype 3
A L Farone1, P C O'Brien, D C Cox
1Department of Microbiology, Miami University, Oxford, Ohio 45056.
Journal of Leukocyte Biology
|February 1, 1993
Summary
Reovirus combined with chemotherapy can reject tumors by inducing tumor-specific immunity. This study shows reovirus stimulates macrophages to release tumor necrosis factor-alpha (TNF-alpha), a key immune mediator.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Reovirus combined with chemotherapy (BCNU) previously showed tumor rejection in mice.
- Surviving mice developed tumor-specific immunity, indicating an immune response.
- The role of peritoneal macrophages in this immune modulation was unexplored.
Purpose of the Study:
- To investigate the interaction between reovirus and murine peritoneal macrophages.
- To determine if this interaction contributes to immune-mediated tumor rejection.
- To elucidate the mechanism of reovirus-induced immune stimulation.
Main Methods:
- In vitro and in vivo studies of reovirus and murine peritoneal macrophages.
- Assessment of macrophage infection by reovirus.
- Measurement of tumor necrosis factor-alpha (TNF-alpha) secretion and membrane expression.
Main Results:
- Reovirus efficiently infected macrophages in vitro, stimulating TNF-alpha secretion.
- In vivo, reovirus did not cause high levels of macrophage infection but induced TNF-alpha expression.
- UV-inactivated reovirus also stimulated TNF-alpha expression, suggesting infection is not required.
Conclusions:
- Reovirus can stimulate peritoneal macrophages to express TNF-alpha.
- TNF-alpha induction by reovirus may be a mechanism for immune stimulation.
- This pathway could contribute to the observed tumor rejection in combination therapy.