Release of nitric oxide during the T cell-independent pathway of macrophage activation
- Washington Univ. School of Medicine, St. Louis, MO (United States)
Immunodeficient mice are remarkably resistant to Listeria monocytogenes (LM) infection. The authors examined the role that nitric oxide (NO) plays in the CB-17/lcr SCID (SCID) response to LM. SCID spleen cells produced large quantities of NO (as measured by nitrite formation) when incubated in the presence of heat-killed LM. NO produced large quantities of nitrite in response to LM, but only in the presence of IFN-[gamma]. The production of NO induced by LM was not affected by neutralizing antibodies to TNF or IL-1. The production of NO was inhibited by addition of either of two inhibitors of NO synthase, N[sup G]-monomethyl arginine, or aminoguanidine. In a different situation, NK cells that were stimulated by TNF and Listeria products to release IFN-[gamma] did not produce NO. Macrophages cultured with IFN-[gamma] killed live LM. This increased killing of LM was significantly inhibited by amino-guanidine. In vivo, administration of aminoguanidine resulted in a marked increase in the mortality and spleen bacterial loads of LM-infected SCID or immunocompetent control mice. It is concluded that NO is a critical effector molecule of T cell-independent natural resistence of LM as studied in the SCID mouse, and that the NO-mediated response is essential for both SCID and immunocompetent host to survive after LM infection. 37 refs., 7 figs.
- OSTI ID:
- 7368825
- Journal Information:
- Journal of Immunology; (United States), Vol. 150:3; ISSN 0022-1767
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
BACTERIA
IMMUNITY
NITRIC OXIDE
BIOLOGICAL EFFECTS
ARGININE
GUANIDINES
INTERFERON
MICE
SPLEEN CELLS
AMINO ACIDS
ANIMAL CELLS
ANIMALS
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACIDS
CHALCOGENIDES
GROWTH FACTORS
LYMPHOKINES
MAMMALS
MICROORGANISMS
MITOGENS
NITROGEN COMPOUNDS
NITROGEN OXIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PROTEINS
RODENTS
SOMATIC CELLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
551000 - Physiological Systems