Role of glutathione in macrophage control of mycobacteria.
Reactive oxygen and nitrogen intermediates are important antimicrobial defense mechanisms of macrophages and other phagocytic cells. While reactive nitrogen intermediates have been shown to play an important role in tuberculosis control in the murine system, their role in human disease is not clearly established. Glutathione, a tripeptide and antioxidant, is synthesized at high levels by cells during reactive oxygen intermediate and nitrogen intermediate production. Glutathione has been recently shown to play an important role in apoptosis and to regulate antigen-presenting-cell functions. Glutathione also serves as a carrier molecule for nitric oxide, in the form of S-nitrosoglutathione. Previous work from this laboratory has shown that glutathione and S-nitrosoglutathione are directly toxic to mycobacteria. A mutant strain of Mycobacterium bovis BCG, defective in the transport of small peptides such as glutathione, is resistant to the toxic effect of glutathione and S-nitrosoglutathione. Using the peptide transport mutant as a tool, we investigated the role of glutathione and S-nitrosoglutathione in animal and human macrophages in controlling intracellular mycobacterial growth.
Venketaraman
Vishwanath
V
Department of Microbiology and Molecular Genetics. New Jersey Medical School National Tuberculosis Center, UMDNJ-New Jersey Medical School, 225 Warren Street, Newark, NJ 07103, USA.
Dayaram
Yaswant K
YK
Amin
Amol G
AG
Ngo
Richard
R
Green
Renee M
RM
Talaue
Meliza T
MT
Mann
Jessica
J
Connell
Nancy D
ND
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D005978:Glutathione / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D017737:Macrophages, Peritoneal / Q000382:microbiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000382:microbiology; D009163:Mycobacterium bovis / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II
D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C037230:oligopeptide permease, Bacteria; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D005978:Glutathione