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Killing of Legionella pneumophila by nitric oxide in γ‐interferon‐activated macrophages
Author(s) -
Summersgill James T.,
Powell Lori A.,
Buster Brad L.,
Miller Richard D.,
Ramirez Julio A.
Publication year - 1992
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.52.6.625
Subject(s) - legionella pneumophila , microbiology and biotechnology , biology , nitric oxide , interferon , intracellular , interferon gamma , incubation , cytokine , bacteria , biochemistry , immunology , genetics , endocrinology
The role of nitric oxide (NO) radicals in killing the intracellular bacterial pathogen Legionella pneumophila (Lp) was examined in infected macrophages. Murine (RAW 264.7) and human (HL‐60) cell monolayers were treated with 100 U/mlγ‐interferon (IFN) and cocultured with Lp in the presence and absence of N G MMA, a specific inhibitor of NO production. Viable Lp in IFN‐treated RAW 264.7 cells decreased from 3.8 to 0.7 ± 0.12 log CFU/ml after 24 h incubation, whereas in IFN + N G MMA‐treated RAW 264.7 cells, viable Lp persisted at 2.2 ± 0.2 log CFU/ml after 24 h. This increased survival corresponded with an inhibition of NO production (5.65 ± 2.99 μ M with N G MMA vs. 58.6 ± 5.36 μ M without N G MMA). Viable Lp were susceptible to killing, in a dose‐dependent fashion, by 0, 2.5, and 5.0 mM sodium nitroprusside, a source of NO radicals. IFN‐treated RAW 264.7 cells also had significantly decreased levels of intracellular iron (below assay limit) when compared to IFN + N G MMA‐treated cells (72.0 ± 0.78 % of control). Normally permissive HL‐60 cells treated with IFN were bacteriostatic rather than bactericidal, and NO production was not detected above background. Thus, NO radicals play a critical role in the bactericidal activity against Lp by IFN‐treated RAW 264.7 cells, but the absence of NO production limits IFN‐treated HL‐60 cells to bac‐ teriostasis.