title: Bacteriostatic activity of BCG/PPD-activated macrophages against Mycobacterium fortuitum does not involve reactive nitrogen or oxygen intermediates.
abstract: Mycobacteria preferentially reside in resident macrophages whereas activated macrophages are presumed to eliminate the bacteria effectively. The aim of the present study was to determine the antibacterial activities of resident and activated murine peritoneal macrophages against Mycobacterium fortuitum and the intracellular mechanisms involved. After phagocytosis M. fortuitum could not be killed by either BCG/PPD-activated and IFN-gamma-activated macrophages and resident macrophages. The mycobacteria did not multiply in BCG/PPD-activated macrophages and the rate of proliferation of M. fortuitum in IFN-gamma-activated macrophages was only slightly inhibited compared to that in resident macrophages. Experiments with selective inhibitors of the production of reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) demonstrated that these factors are not essential for the mycobacteriostatic activity of BCG/PPD-activated macrophages. After phagocytosis of M. fortuitum, BCG/PPD-activated and IFN-gamma-activated macrophages produced substantial amounts of both RNI and ROI. No correlation was found between the levels of these intermediates and the proliferation of M. fortuitum in the macrophages. In conclusion, BCG/PPD-activated macrophages are bacteriostatic, but not bacteriocidal for M. fortuitum and the former does not involve reactive nitrogen and oxygen intermediates.
authors.affiliation: Department of Infectious Diseases, University Hospital Leiden, The Netherlands.
authors.forename: P H
authors.initials: PH
authors.lastname: Nibbering
authors.forename: S I
authors.initials: SI
authors.lastname: Yoshida
authors.forename: M T
authors.initials: MT
authors.lastname: van den Barselaar
authors.forename: R
authors.initials: R
authors.lastname: van Furth
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002455:Cell Division; D008262:Macrophage Activation / Q000502:physiology*; D008297:Male; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009170:Nontuberculous Mycobacteria / Q000276:immunology*; D010587:Phagocytosis / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014373:Tuberculin / Q000276:immunology; D019323:omega-N-Methylarginine
chemical_list: D017382:Reactive Oxygen Species; D014373:Tuberculin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine