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Altered immune responses in mice lacking inducible nitric oxide synthase.

TitleAltered immune responses in mice lacking inducible nitric oxide synthase.
Publication TypeJournal Article
Year of Publication1995
AuthorsWei XQ, Charles IG, Smith A, Ure J, Feng GJ, Huang FP, Xu D, Muller W, Moncada S, Liew FY
JournalNature
Volume375
Issue6530
Pagination408-11
Date Published1995 Jun 1
ISSN0028-0836
KeywordsAmino Acid Oxidoreductases, Animals, Carrageenan, Cells, Cultured, Chimera, Cytokines, Immune System, Immunity, Innate, Leishmania major, Leishmaniasis, Cutaneous, Lipopolysaccharides, Macrophages, Peritoneal, Mice, Mutagenesis, Nitric Oxide Synthase, Spleen, T-Lymphocyte Subsets, T-Lymphocytes, Helper-Inducer
Abstract

Nitric oxide (NO) is important in many biological functions. It is generated from L-arginine by the enzyme NO synthase (NOS). The cytokine-inducible NOS (iNOS) is activated by several immunological stimuli, leading to the production of large quantities of NO which can be cytotoxic. To define the biological role of iNOS further, we generated iNOS mutant mice. These are viable, fertile and without evident histopathological abnormalities. However, in contrast to wild-type and heterozygous mice, which are highly resistant to the protozoa parasite Leishmania major infection, mutant mice are uniformly susceptible. The infected mutant mice developed a significantly stronger Th1 type of immune response than the wild-type or heterozygous mice. The mutant mice showed reduced nonspecific inflammatory response to carrageenin, and were resistant to lipopolysaccharide-induced mortality.

DOI10.1038/375408a0
Alternate JournalNature
PubMed ID7539113
Grant List / / Wellcome Trust / United Kingdom