Journal of Leukocyte Biology, Vol 49, Issue 4 380-387, Copyright © 1991 by Society for Leukocyte Biology
JOURNAL ARTICLE |
M Denis
Centre de pneumologie, Hopital Laval, Sainte-Foy, Quebec, Canada.
An avirulent and a virulent strain of Mycobacterium avium were selected on the basis of their growth patterns in human monocyte-derived macrophages. The virulent 7497 M. avium grew progressively in untreated macrophages, whereas the avirulent LR/149 M. avium was killed to a moderate extent by untreated human macrophages (50% of the original infectious inoculum killed 7 days after infection). We set out to investigate the possibility of modulating these growth patterns by cytokine treatment. Application of tumor necrosis factor (TNF) (100 U/ml) led to macrophages restricting significantly the growth of virulent M. avium 7497 (tenfold decrease at 7 days). TNF was also effective at modulating positively the interaction between avirulent LR/149 M. avium and macrophages inasmuch as TNF-treated cells killed 99% of infecting mycobacteria at 7 days. Granulocyte macrophage-colony stimulating factor (GM-CSF) (100-10,000 U/ml) treatment led to macrophages being as mycobacteriostatic for virulent 7497 M. avium as TNF-alpha-treated cells (i.e., tenfold reduction in growth). Treatment of macrophages with both GM-CSF and TNF-alpha was shown to have additive effects on bacteriostatic activity on M. avium. The mechanism of killing of avirulent M. avium by TNF-alpha was shown to be dependent on the generation of reactive nitrogen intermediates, as seen by inhibition of effector mechanisms by NG-monomethyl-arginine and arginase. Moreover, there was a correlation between NO2- generation and mycobactericidal activity of macrophages. Addition of superoxide dismutase reversed the killing of avirulent M. avium by untreated or TNF-treated macrophages. This abrogation was also apparent in chronic granulomatous disease (CGD) macrophages, which were inefficient at generating reactive oxygen intermediates. Moreover, macrophages from CGD patients killed avirulent M. avium as efficiently as cells from normal individuals. We conclude from these results that 1) GM-CSF and TNF-alpha, alone or in combination, increase effector functions of macrophages against virulent and avirulent strains of M. avium; 2) reactive nitrogen intermediates seem to be involved in this effector mechanism; and 3) superoxide dismutase protected M. avium against macrophage effector function, seemingly by protecting the bacteria against endogenous superoxide anion. The implications of these findings for host resistance to atypical mycobacteria are discussed.
This article has been cited by other articles:
 |
|
 |
|
  S. B. Sable, D. Goyal, I. Verma, D. Behera, and G. K. Khuller Lung and blood mononuclear cell responses of tuberculosis patients to mycobacterial proteins Eur. Respir. J., February 1, 2007; 29(2): 337 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Murphey, D. N. Herndon, and E. R. Sherwood Gamma Interferon Does Not Enhance Clearance of Pseudomonas aeruginosa but Does Amplify a Proinflammatory Response in a Murine Model of Postseptic Immunosuppression Infect. Immun., December 1, 2004; 72(12): 6892 - 6901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Raju, Y. Hoshino, K. Kuwabara, I. Belitskaya, S. Prabhakar, A. Canova, J. A. Gold, R. Condos, R. I. Pine, S. Brown, et al. Aerosolized Gamma Interferon (IFN-{gamma}) Induces Expression of the Genes Encoding the IFN-{gamma}-Inducible 10-Kilodalton Protein but Not Inducible Nitric Oxide Synthase in the Lung during Tuberculosis Infect. Immun., March 1, 2004; 72(3): 1275 - 1283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Schroder, P. J. Hertzog, T. Ravasi, and D. A. Hume Interferon-{gamma}: an overview of signals, mechanisms and functions J. Leukoc. Biol., February 1, 2004; 75(2): 163 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-J. Cardona, S. Gordillo, J. Diaz, G. Tapia, I. Amat, A. Pallares, C. Vilaplana, A. Ariza, and V. Ausina Widespread Bronchogenic Dissemination Makes DBA/2 Mice More Susceptible than C57BL/6 Mice to Experimental Aerosol Infection with Mycobacterium tuberculosis Infect. Immun., October 1, 2003; 71(10): 5845 - 5854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Briscoe, D. R. Roach, N. Meadows, D. Rathjen, and W. J. Britton A novel tumor necrosis factor (TNF) mimetic peptide prevents recrudescence of Mycobacterium bovis bacillus Calmette-Guerin (BCG) infection in CD4+ T cell-depleted mice J. Leukoc. Biol., October 1, 2000; 68(4): 538 - 544. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. M. Coccia, E. Stellacci, G. Marziali, G. Weiss, and A. Battistini IFN-{gamma} and IL-4 differently regulate inducible NO synthase gene expression through IRF-1 modulation Int. Immunol., July 1, 2000; 12(7): 977 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Meydani and W.-K. Ha Immunologic effects of yogurt Am. J. Clinical Nutrition, April 1, 2000; 71(4): 861 - 872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mori, Y. Nunokawa, Y. Yamada, S. Ikeda, M. Tomonaga, and N. Yamamoto Expression of Human Inducible Nitric Oxide Synthase Gene in T-Cell Lines Infected With Human T-Cell Leukemia Virus Type-I and Primary Adult T-Cell Leukemia Cells Blood, October 15, 1999; 94(8): 2862 - 2870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Nau, L. Liaw, G. L. Chupp, J. S. Berman, B. L. M. Hogan, and R. A. Young Attenuated Host Resistance against Mycobacterium bovis BCG Infection in Mice Lacking Osteopontin Infect. Immun., August 1, 1999; 67(8): 4223 - 4230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hayashi, S. P. Rao, P. R. Meylan, R. S. Kornbluth, and A. Catanzaro Role of CD40 Ligand in Mycobacterium avium Infection Infect. Immun., July 1, 1999; 67(7): 3558 - 3565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ekman, M. Saarinen, Q. He, M. Virtala, M. Salmi, and K. Granfors Human Monocytic U937 Cells Kill Salmonella In Vitro by NO-Independent Mechanisms Infect. Immun., July 1, 1999; 67(7): 3670 - 3673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Y. Haddad, A. Panoskaltsis-Mortari, D. H. Ingbar, S. Yang, C. E. Milla, and B. R. Blazar High Levels of Peroxynitrite Are Generated in the Lungs of Irradiated Mice Given Cyclophosphamide and Allogeneic T Cells . A Potential Mechanism of Injury after Marrow Transplantation Am. J. Respir. Cell Mol. Biol., June 1, 1999; 20(6): 1125 - 1135. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. BONAY, F. BOUCHONNET, V. PELICIC, B. LAGIER, M. GRANDSAIGNE, D. LECOSSIER, A. GRODET, M. VOKURKA, B. GICQUEL, and A. J. HANCE Effect of Stimulation of Human Macrophages on Intracellular Survival of Mycobacterium bovis Bacillus Calmette-Guerin . Evaluation with a Mycobacterial Reporter Strain Am. J. Respir. Crit. Care Med., May 1, 1999; 159(5): 1629 - 1637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. MacFarlane, M. G. Schwacha, and T. K. Eisenstein In Vivo Blockage of Nitric Oxide with Aminoguanidine Inhibits Immunosuppression Induced by an Attenuated Strain of Salmonella typhimurium, Potentiates Salmonella Infection, and Inhibits Macrophage and Polymorphonuclear Leukocyte Influx into the Spleen Infect. Immun., February 1, 1999; 67(2): 891 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Garbe, N. S. Hibler, and V. Deretic Response to Reactive Nitrogen Intermediates in Mycobacterium tuberculosis: Induction of the 16-Kilodalton alpha -Crystallin Homolog by Exposure to Nitric Oxide Donors Infect. Immun., January 1, 1999; 67(1): 460 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Villalta, Y. Zhang, K. E. Bibb, J. C. Kappes, and M. F. Lima The Cysteine-Cysteine Family of Chemokines RANTES, MIP-1alpha , and MIP-1beta Induce Trypanocidal Activity in Human Macrophages via Nitric Oxide Infect. Immun., October 1, 1998; 66(10): 4690 - 4695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O. Fontt, P. De Baetselier, C. Heirman, K. Thielemans, R. Lucas, and B. Vray Effects of Granulocyte-Macrophage Colony-Stimulating Factor and Tumor Necrosis Factor Alpha on Trypanosoma cruzi Trypomastigotes Infect. Immun., June 1, 1998; 66(6): 2722 - 2727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Britton, N. Meadows, D. A. Rathjen, D. R. Roach, and H. Briscoe A Tumor Necrosis Factor Mimetic Peptide Activates a Murine Macrophage Cell Line To Inhibit Mycobacterial Growth in a Nitric Oxide-Dependent Fashion Infect. Immun., May 1, 1998; 66(5): 2122 - 2127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kim, O. Bang, Y. Lee, and S. Kang Production of inducible nitric oxide is required for monocytic differentiation of U937 cells induced by vitamin E-succinate J. Cell Sci., January 2, 1998; 111(4): 435 - 441. [Abstract] [PDF]
|
|
|
|
|
|
G. C. BALDWIN, D. P. TASHKIN, D. M. BUCKLEY, A. N. PARK, S. M. DUBINETT, and M. D. ROTH Marijuana and Cocaine Impair Alveolar Macrophage Function and Cytokine Production Am. J. Respir. Crit. Care Med., November 1, 1997; 156(5): 1606 - 1613. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. D. MacMicking, R. J. North, R. LaCourse, J. S. Mudgett, S. K. Shah, and C. F. Nathan Identification of nitric oxide synthase as a protective locus against tuberculosis PNAS, May 13, 1997; 94(10): 5243 - 5248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Hashimoto, M. Yamada, K. Motoyoshi, and K. S. Akagawa Enhancement of Macrophage Colony-Stimulating Factor-Induced Growth and Differentiation of Human Monocytes by Interleukin-10 Blood, January 1, 1997; 89(1): 315 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Arias-Diaz, E. Vara, C. Garcia, N. Villa, and J. L. Balibrea Evidence for a Cyclic Guanosine Monophosphate--Dependent, Carbon Monoxide--Mediated, Signaling System in the Regulation of TNF-{alpha} Production by Human Pulmonary Macrophages Arch Surg, December 1, 1995; 130(12): 1287 - 1293. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Moncada and A. Higgs The L-Arginine-Nitric Oxide Pathway N. Engl. J. Med., December 30, 1993; 329(27): 2002 - 2012. [Full Text]
|
|
