Role of reactive nitrogen and oxygen intermediates in gamma interferon-stimulated murine macrophage bactericidal activity against Burkholderia pseudomallei

We examined the contributions of reactive nitrogen and oxygen intermediates (RNI and ROI, respectively) in macrophage bactericidal activity against Burkholderia pseudomallei, the causative agent of melioidosis, in order to understand host defense mechanisms against infection caused by this bacterium. The bacteria multiplied in unstimulated murine macrophage cell line J774.1. However, a strong dose-dependent inhibition of intracellular bacterial growth was observed when gamma interferon (IFN-gamma)-activated macrophages were used. The induction of bactericidal activity correlated well with the production of nitric oxide (NO) by IFN-gamma-activated macrophages and was markedly suppressed by N(G)-monomethyl L-arginine (L-NMMA), a competitive inhibitor of NO synthesis. Superoxide dismutase (SOD) and catalase significantly inhibited macrophage bactericidal activity, and the combined addition of L-NMMA, SOD, and catalase resulted in the complete inhibition of IFN-gamma-stimulated activity. The bacteria were susceptible to the killing effects of chemically generated NO and superoxide anion in a macrophage-free system. Our results indicate that IFN-gamma-induced macrophage bactericidal activity against B. pseudomallei is mediated to a large extent by RNI killing mechanisms and to a lesser extent by ROI-dependent mechanisms.

[1]  A. Jones,et al.  Intracellular survival of Burkholderia pseudomallei , 1996, Infection and immunity.

[2]  K. Kawakami,et al.  Enhancing effect of oxygen radical scavengers on murine macrophage anticryptococcal activity through production of nitric oxide , 1996, Clinical and experimental immunology.

[3]  D. Clemens,et al.  Characterization of the Mycobacterium tuberculosis phagosome. , 1996, Trends in microbiology.

[4]  D. Wink,et al.  Modulation of Superoxide-dependent Oxidation and Hydroxylation Reactions by Nitric Oxide (*) , 1996, The Journal of Biological Chemistry.

[5]  浩 普久原.  Efficacy of Antibiotics against Extracellular and Intracellular Burkholderia Pseudomallei,and their Therapeutic Effects on Experimental Pneumonia in Mice , 1995 .

[6]  A. Casadevall,et al.  Susceptibility of melanized and nonmelanized Cryptococcus neoformans to nitrogen- and oxygen-derived oxidants , 1994, Infection and immunity.

[7]  R. Johns,et al.  Inhibition of nitric oxide synthase by a superoxide generating system. , 1993, The Journal of pharmacology and experimental therapeutics.

[8]  E. Yabuuchi,et al.  Burkholderia pseudomallei and Melioidosis: Be Aware in Temperate Area , 1993, Microbiology and immunology.

[9]  N. White,et al.  Relapse in melioidosis: incidence and risk factors. , 1993, The Journal of infectious diseases.

[10]  A. Sher,et al.  The microbicidal activity of interferon‐γ‐treated macrophages against Trypanosoma cruzi involves an L‐arginine‐dependent, nitrogen oxide‐mediated mechanism inhibitable by interleukin‐10 and transforming growth factor‐β , 1992, European journal of immunology.

[11]  S. Abramson,et al.  Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase. , 1992, The Journal of clinical investigation.

[12]  B. Bloom,et al.  Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages , 1992, The Journal of experimental medicine.

[13]  M. Wilson,et al.  Production of hydroxyl radicals from the simultaneous generation of superoxide and nitric oxide. , 1992, The Biochemical journal.

[14]  S. Franzblau,et al.  L-arginine-dependent macrophage effector functions inhibit metabolic activity of Mycobacterium leprae. , 1991, Journal of immunology.

[15]  M. Denis.  Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates. , 1991, Cellular immunology.

[16]  I. Polacheck,et al.  Catecholamines and virulence of Cryptococcus neoformans , 1990, Infection and immunity.

[17]  S. Moncada,et al.  Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. , 1990, Journal of immunology.

[18]  S. Pruksachartvuthi,et al.  Survival of Pseudomonas pseudomallei in human phagocytes. , 1990, Journal of medical microbiology.

[19]  J. Perfect,et al.  Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages. , 1990, The Journal of clinical investigation.

[20]  S. James,et al.  Macrophage cytotoxicity against schistosomula of Schistosoma mansoni involves arginine-dependent production of reactive nitrogen intermediates. , 1989, Journal of immunology.

[21]  N. White,et al.  HALVING OF MORTALITY OF SEVERE MELIOIDOSIS BY CEFTAZIDIME , 1989, The Lancet.

[22]  N. White,et al.  Melioidosis: a major cause of community-acquired septicemia in northeastern Thailand. , 1989, The Journal of infectious diseases.

[23]  A. Leelarasamee,et al.  Melioidosis: review and update. , 1989, Reviews of infectious diseases.

[24]  J. Hibbs,et al.  Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. , 1987, Science.

[25]  R. Guard,et al.  The prevalence of human melioidosis in Northern Queensland. , 1984, The American journal of tropical medicine and hygiene.

[26]  R. Guard,et al.  Melioidosis in Far North Queensland. A clinical and epidemiological review of twenty cases. , 1984, The American journal of tropical medicine and hygiene.

[27]  E. Mays,et al.  Melioidosis: recrudescence associated with bronchogenic carcinoma twenty-six years following initial geographic exposure. , 1975, Chest.

[28]  K. Rajagopalan,et al.  The role of superoxide anion generation in phagocytic bactericidal activity. Studies with normal and chronic granulomatous disease leukocytes. , 1975, The Journal of clinical investigation.

[29]  B. Babior,et al.  Biological defense mechanisms. Evidence for the participation of superoxide in bacterial killing by xanthine oxidase. , 1975, The Journal of laboratory and clinical medicine.

[30]  S. Klebanoff,et al.  Role of the superoxide anion in the myeloperoxidase-mediated antimicrobial system. , 1974, The Journal of biological chemistry.