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Altered immune responses in mice lacking inducible nitric oxide synthase
X Q Wei1, I G Charles, A Smith
1Department of Immunology, University of Glasgow, UK.
Nature
|June 1, 1995
Summary
Mice lacking inducible nitric oxide synthase (iNOS) are susceptible to Leishmania major infection, indicating iNOS is crucial for host defense against this parasite. These iNOS-deficient mice exhibit altered immune responses and inflammation.
Area of Science:
- Immunology
- Molecular Biology
- Parasitology
Background:
- Nitric oxide (NO) plays a vital role in numerous biological processes.
- The enzyme nitric oxide synthase (NOS) produces NO from L-arginine.
- Cytokine-inducible NOS (iNOS) produces large amounts of NO upon immune stimulation, which can be cytotoxic.
Purpose of the Study:
- To elucidate the biological functions of iNOS.
- To investigate the role of iNOS in host defense mechanisms.
- To characterize the immune response in iNOS-deficient mice.
Main Methods:
- Generation of iNOS mutant mice.
- Assessment of parasite susceptibility (Leishmania major).
- Evaluation of immune responses (Th1) and inflammatory markers (carrageenin, lipopolysaccharide).
Main Results:
- iNOS mutant mice are susceptible to Leishmania major infection, unlike resistant wild-type and heterozygous mice.
- Mutant mice display a heightened Th1 immune response.
- Reduced nonspecific inflammatory responses to carrageenin and resistance to lipopolysaccharide-induced mortality were observed in mutant mice.
Conclusions:
- Inducible nitric oxide synthase (iNOS) is essential for resistance to Leishmania major infection.
- iNOS plays a significant role in modulating Th1 immune responses and inflammatory processes.
- iNOS-deficient mice provide a valuable model for studying host-pathogen interactions and immune regulation.