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Activation of phagocytic cell NADPH oxidase by norfloxacin: a potential mechanism to explain its bactericidal action
Author(s) -
El Bekay Rajaa,
Álvarez Moisés,
Carballo Modesto,
MartínNieto José,
Monteseirín Javier,
Pintado Elizabeth,
Bedoya Francisco J.,
Sobrino Francisco
Publication year - 2002
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 - 10.1189/jlb.71.2.255
Subject(s) - norfloxacin , nadph oxidase , superoxide , intracellular , lucigenin , reactive oxygen species , biology , microbiology and biotechnology , antibacterial agent , oxidase test , phagocytosis , mechanism of action , cytosol , antibiotics , biochemistry , in vitro , enzyme , ciprofloxacin
The mechanisms underlying the bactericidal power of fluoroquinolones against intracellular parasites in host macrophages remain poorly understood. We have analyzed the effect of norfloxacin, a fluoroquinolone antibiotic, on the production of reactive oxygen intermediates (O 2 •− and H 2 O 2 ) and NADPH oxidase activity in mouse macrophages. The generation of anion superoxide (O 2 •− ) was found to be significantly greater in macrophages incubated with norfloxacin than in untreated controls. This enhancing effect of norfloxacin was dose‐dependent and reached maximal values within 10 min after its addition. The O 2 •− generated was mainly intracellular, as determined by the use of specific dyes, such as lucigenin and luminol, and able to diffuse freely through the cell membrane. Also, the production of H 2 O 2 was increased in macrophages in response to norfloxacin. The positive effect of norfloxacin was associated to an enhanced mobilization of NADPH oxidase subunits p47 phox and p67 phox from the cytosol to the plasma membrane in phagocytic cells. The effect of the antibiotic persisted in vivo for several hours. These data support the notion that norfloxacin inhibits mycobacterial growth within phagocytic cells by enhancing intracellular production of O 2 •− and other reactive oxygen species.