title: Release of nitric oxide during the T cell-independent pathway of macrophage activation. Its role in resistance to Listeria monocytogenes.
abstract: Immunodeficient mice are remarkably resistant to Listeria monocytogenes (LM) infection. We 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. production was dependent on the release of IFN-gamma by the SCID NK cells. When tested directly, macrophages 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, NG-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. We conclude that NO. is a critical effector molecule of T cell-independent natural resistance to 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.
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: K P
authors.initials: KP
authors.lastname: Beckerman
authors.forename: H W
authors.initials: HW
authors.lastname: Rogers
authors.forename: J A
authors.initials: JA
authors.lastname: Corbett
authors.forename: R D
authors.initials: RD
authors.lastname: Schreiber
authors.forename: M L
authors.initials: ML
authors.lastname: McDaniel
authors.forename: E R
authors.initials: ER
authors.lastname: Unanue
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006146:Guanidines / Q000494:pharmacology; D007371:Interferon-gamma / Q000502:physiology; D008088:Listeriosis / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D006146:Guanidines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C004479:pimagedine