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Nitric oxide induction by pertussis toxin in mouse spleen cells via gamma interferon
S Sakurai1, K Kamachi, T Konda
1Department of Bacterial and Blood Products, National Institute of Health, Tokyo, Japan.
Abstract:
We examined the major pathogenic substances of Bordetella pertussis for the ability to induce nitric oxide, and important biological function of macrophages, via gamma interferon in spleen cells. B. pertussis, which produces a variety of pathogenic substances, including pertussis toxin and filamentous hemagglutinin, causes a severe respiratory disease. Nitric oxide was detected in the culture fluid of spleen cells stimulated with pertussis toxin or its B oligomer but not in the culture fluid of spleen cells stimulated with the A protomer of pertussis toxin or with filamentous hemagglutinin. Incubation of the peritoneal exudate macrophages with pertussis toxin, B oligomer, A protomer, or filamentous hemagglutinin induced little nitric oxide, whereas incubation with gamma interferon induced a significant amount of nitric oxide. The induction of nitric oxide in spleen cells stimulated with pertussis toxin was completely inhibited by anti-gamma interferon antibody. The treatment of spleen cells with anti-Thy-1.2 antibody plus complement followed by stimulation with pertussis toxin decreased the secretion of gamma interferon and nitric oxide. These results suggest that gamma interferon from T lymphocytes stimulated with pertussis toxin induces nitric oxide.
Insights
Pertussis toxin from Bordetella pertussis stimulates T lymphocytes to produce gamma interferon, which then induces nitric oxide production in spleen cells, crucial for macrophage function.
Area of Science:
- Immunology
- Microbiology
Background:
- Bordetella pertussis causes severe respiratory illness.
- Key virulence factors include pertussis toxin and filamentous hemagglutinin.
Purpose of the Study:
- To investigate how Bordetella pertussis pathogenic substances induce nitric oxide (NO) production.
- To understand the role of gamma interferon (IFN-γ) in this process within spleen cells.
Main Methods:
- Spleen cells were stimulated with pertussis toxin (PT) and its components (B oligomer, A protomer), and filamentous hemagglutinin (FHA).
- Nitric oxide production was measured in culture fluids.
- Macrophages were incubated with stimulants, and IFN-γ's role was assessed using antibodies and cell depletion.
Main Results:
- Pertussis toxin and its B oligomer, but not the A protomer or FHA, induced NO in spleen cells.
- Direct stimulation of macrophages with PT components or FHA yielded minimal NO; gamma interferon induced significant NO.
- Anti-gamma interferon antibody completely blocked NO induction by PT.
- Depletion of T lymphocytes reduced IFN-γ and NO secretion.
Conclusions:
- Pertussis toxin stimulates T lymphocytes to produce gamma interferon.
- Gamma interferon induced by pertussis toxin is responsible for nitric oxide production in spleen cells.
- This pathway highlights a mechanism of immune modulation by Bordetella pertussis.
