Comparison of control of Listeria by nitric oxide redox chemistry from murine macrophages and NO donors: insights into listeriocidal activity of oxidative and nitrosative stress.
The physiological function of nitric oxide (NO) in the defense against pathogens is multifaceted. The exact chemistry by which NO combats intracellular pathogens such as Listeria monocytogenes is yet unresolved. We examined the effects of NO exposure, either delivered by NO donors or generated in situ within ANA-1 murine macrophages, on L. monocytogenes growth. Production of NO by the two NONOate compounds PAPA/NO (NH2(C3H6)(N[N(O)NO]C3H7) and DEA/NO (Na(C2H5)2N[N(O)NO]) resulted in L. monocytogenes cytostasis with minimal cytotoxicity. Reactive oxygen species generated from xanthine oxidase/hypoxanthine were neither bactericidal nor cytostatic and did not alter the action of NO. L. monocytogenes growth was also suppressed upon internalization into ANA-1 murine macrophages primed with interferon-gamma (INF-gamma) + tumor necrosis factor-alpha (TNF-alpha or INF-gamma + lipid polysaccharide (LPS). Growth suppression correlated with nitrite formation and nitrosation of 2,3-diaminonaphthalene elicited by stimulated murine macrophages. This nitrosative chemistry was not dependent upon nor mediated by interaction with reactive oxygen species (ROS), but resulted solely from NO and intermediates related to nitrosative stress. The role of nitrosation in controlling L. monocytogenes was further examined by monitoring the effects of exposure to NO on an important virulence factor, Listeriolysin O, which was inhibited under nitrosative conditions. These results suggest that nitrosative stress mediated by macrophages is an important component of the immunological arsenal in controlling L. monocytogenes infections.
Ogawa
R
R
Radiation Biology Branch, NIH/National Cancer Institute, Building 10, Room B3-B69, Bethesda, MD 20892, USA.
Pacelli
R
R
Espey
M G
MG
Miranda
K M
KM
Friedman
N
N
Kim
S M
SM
Cox
G
G
Mitchell
J B
JB
Wink
D A
DA
Russo
A
A
D015081:2-Naphthylamine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006834:Hydrazines / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000187:drug effects / Q000254:growth & development*; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D006834:Hydrazines; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D009573:Nitrites; C112653:PAPA NONOate; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019820:Xanthine; C026373:2,3-diaminonaphthalene; D009569:Nitric Oxide; D007371:Interferon-gamma; D015081:2-Naphthylamine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D014969:Xanthine Oxidase