Mycobacterium lepraemurium activates macrophages but fails to trigger release of superoxide anion.
Mycobacterium lepraemurium failed to stimulate a normal respiratory burst when presented to mouse peritoneal or bone marrow macrophages. By comparison, Mycobacterium bovis (strain Bacillus Calmette-Guerin) or Saccharomyces cerevisiae, as expected, stimulated macrophages to release a large amount of superoxide anion (O2-). M. lepraemurium did not interfere with the response to yeast when both microbes were added together to macrophages. The low release of O2- induced by M. lepraemurium was not due to failure of M. lepraemurium to activate or prime macrophages, because exposure of macrophages to M. lepraemurium caused the expected enhancement of O2- release when the macrophages were stimulated by PMA. Similarly, macrophages taken from mice infected with M. lepraemurium were activated, as indicated by high PMA-stimulated O2- release. Macrophages primed in vitro by exposure to Escherichia coli LPS for 24 h did show a moderate O2- response when stimulated by M. lepraemurium, but macrophages primed by exposure to IFN-gamma muramyl dipeptide, or M. lepraemurium showed a weak response when subsequently challenged with M. lepraemurium. The priming effect of M. lepraemurium or LPS decreased substantially after macrophages were cultured in fresh medium for 24 h. Heat killing or opsonization of M. lepraemurium caused the M. lepraemurium to stimulate a high amount of O2- release from LPS-primed macrophages, but heat killing or opsonization of M. lepraemurium had no effect on release of O2- from unprimed macrophages. The results suggest that M. lepraemurium is taken into macrophages by a mechanism that bypasses the FcR and other receptors that are capable of triggering the production of O2-.
Mor
N
N
Department of Molecular and Cellular Biology, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Goren
M B
MB
Pabst
M J
MJ
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009164:Mycobacterium Infections / Q000276:immunology* / Q000378:metabolism; D009167:Mycobacterium lepraemurium / Q000276:immunology*; D010587:Phagocytosis; D013481:Superoxides / Q000378:metabolism*
D008070:Lipopolysaccharides; D013481:Superoxides