scholarly journals Differential expression of inducible nitric oxide synthase and IL-12 between peritoneal and splenic macrophages stimulated with LPS plus IFN-γ is associated with the activation of extracellular signal-related kinase

2006 ◽  
Vol 18 (6) ◽  
pp. 981-990 ◽  
Author(s):  
Yi-Na Zhu ◽  
Yi-Fu Yang ◽  
Shiro Ono ◽  
Xiang-Gen Zhong ◽  
Yong-Hong Feng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Differential Expression ◽  
Inducible Nitric Oxide Synthase ◽  
Splenic Macrophages ◽  
Extracellular Signal ◽  
Ifn Γ ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Both Inducible Nitric Oxide Synthase and NADPH Oxidase Contribute to the Control of Virulent Phase I Coxiella burnetii Infections

2004 ◽  
Vol 72 (11) ◽  
pp. 6666-6675 ◽  
Author(s):  
Robert E. Brennan ◽  
Kasi Russell ◽  
Guoquan Zhang ◽  
James E. Samuel
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cell Lines ◽  
Inducible Nitric Oxide Synthase ◽  
Coxiella Burnetii ◽  
Wild Type ◽  
Primary Mouse ◽  
Ifn Γ ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Host control of Coxiella burnetii infections is believed to be mediated primarily by activated monocytes/macrophages. The activation of macrophages by cytokines leads to the production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) that have potent antimicrobial activities. The contributions of ROI and RNI to the inhibition of C. burnetii replication were examined in vitro by the use of murine macrophage-like cell lines and primary mouse macrophages. A gamma interferon (IFN-γ) treatment of infected cell lines and primary macrophages resulted in an increased production of nitric oxide (NO) and hydrogen peroxide (H2O2) and a significant inhibition of C. burnetii replication. The inhibition of replication was reversed in the murine cell line J774.16 upon the addition of either the inducible nitric oxide synthase (iNOS) inhibitor NG-monomethyl-l-arginine (NGMMLA) or the H2O2 scavenger catalase. IFN-γ-treated primary macrophages from iNOS−/− and p47phox−/− mice significantly inhibited replication but were less efficient at controlling infection than IFN-γ-treated wild-type macrophages. To investigate the contributions of ROI and RNI to resistance to infection, we performed in vivo studies, using C57BL/6 wild-type mice and knockout mice lacking iNOS or p47phox. Both iNOS−/− and p47phox−/− mice were attenuated in the ability to control C. burnetii infection compared to wild-type mice. Together, these results strongly support a role for both RNI and ROI in the host control of C. burnetii infection.

scholarly journals αβ T Cell Receptor-positive Cells and Interferon-γ, but not Inducible Nitric Oxide Synthase, Are Critical for Granuloma Necrosis in a Mouse Model of Mycobacteria-induced Pulmonary Immunopathology

2001 ◽  
Vol 194 (12) ◽  
pp. 1847-1859 ◽  
Author(s):  
Stefan Ehlers ◽  
Jochen Benini ◽  
Heinz-Dieter Held ◽  
Christiane Roeck ◽  
Gottfried Alber ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cell ◽  
Nitric Oxide Synthase ◽  
T Cell Receptor ◽  
Inducible Nitric Oxide Synthase ◽  
Bacterial Load ◽  
Cell Receptor ◽  
Ifn Γ ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The immunological basis of tuberculin-induced necrosis, known for more than a century as “Koch's phenomenon,” remains poorly understood. Aerosol infection in mice with the highly virulent Mycobacterium avium strain TMC724 causes progressive pulmonary pathology strongly resembling caseating necrosis in human patients with tuberculosis. To identify the cellular and molecular mediators causing this pathology, we infected C57BL/6 mice and mice selectively deficient in recombinase activating gene (RAG)-1, αβ T cell receptor (TCR), γδ TCR, CD4, CD8, β2-microglobulin, interferon (IFN)-γ, interleukin (IL)-10, IL-12p35, IL-12p35/p40, or iNOS with M. avium by aerosol and compared bacterial multiplication, histopathology, and respiratory physiology in these mice. The bacterial load in the lung was similarly high in all mouse groups. Pulmonary compliance, as a surrogate marker for granulomatous infiltrations in the lung, deteriorated to a similar extent in all groups of mice, except in αβ TCR-knockout (KO) and IL-12–KO mice in which compliance was higher, and in IFN-γ and inducible nitric oxide synthase–KO mice in which compliance was reduced faster. Progressive caseation of pulmonary granulomas never occurred in αβ TCR-KO, IL-12–KO, and IFN-γ–KO mice and was reduced in CD4-KO mice. In summary, αβ TCR+ cells and IFN-γ are essential for the development of mycobacteria-induced pulmonary caseous necrosis. In contrast, high mycobacterial load and extensive granulomatous infiltration per se are not sufficient to cause caseation, nor is granuloma necrosis linked to the induction of nitric oxide.

scholarly journals Defective Nitric Oxide Effector Functions Lead to Extreme Susceptibility of Trypanosoma cruzi-Infected Mice Deficient in Gamma Interferon Receptor or Inducible Nitric Oxide Synthase

1998 ◽  
Vol 66 (3) ◽  
pp. 1208-1215 ◽  
Author(s):  
Christoph Hölscher ◽  
Gabriele Köhler ◽  
Uwe Müller ◽  
Horst Mossmann ◽  
Günter A. Schaub ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Specific Antibody ◽  
Mutant Mouse ◽  
Antibody Responses ◽  
Mouse Strains ◽  
Ifn Γ ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Trypanosoma cruzi, the causative agent of Chagas’ disease, induces an innate and adaptive host immune response during the acute phase of infection. These responses were analyzed by comparing mouse lines deficient for the gamma interferon (IFN-γ) receptor (IFN-γR−/−) or deficient for inducible nitric oxide synthase (iNOS−/−). Both lines were highly susceptible, with similar and dramatically increased parasite burdens and severe histopathology and were incapable of surviving even very low doses, exhibiting similar mortality kinetics. This pathophysiological correlation has a common cause, since both mutant mouse strains were unable to respond to infection by producing nitric oxide (NO) with the consequence that mutant macrophages had impaired trypanocidal activities. These in vivo and subsequent in vitro studies further demonstrated that an IFN-γ-dependent pathway of iNOS induction is crucial for efficient NO production and mandatory for resisting acute infection with T. cruzi. Despite this defect, both mutant mouse strains had a rather normal proinflammatory cytokine response (interleukin-12 [IL-12], IFN-γ, IL-6), with the exception of an impaired tumor necrosis factor alpha and IL-1α response in IFN-γR−/− mice, demonstrating that only the latter two cytokines are dependent on IFN-γ activation. Moreover, polarization of T cells in type 1 and type 2 T-helper (Th1/Th2) and cytotoxic T (Tc1/Tc2) cells as well as T. cruzi-specific antibody responses were normal in IFN-γR−/− mice, demonstrating that IFN-γ is not necessary for the promotion of T-cell differentiation and T. cruzi-specific antibody responses.

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