* Departamento de Bioquímica Médica y Biología Molecular, and
Servicio de Inmunología y Alergia, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Spain; and
Division de Genética, Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, Spain
Correspondence: Francisco Sobrino, Departamento de Bioquímica Médica y Biología Molecular, Facultad de Medicina, Av. Sánchez Pizjuán 4, E-41009 Sevilla, Spain. E-mail: fsobrino{at}cica.es
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 (O2•- and H2O2) and NADPH oxidase activity in mouse macrophages. The generation of anion superoxide (O2•-) 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 O2•- 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 H2O2 was increased in macrophages in response to norfloxacin. The positive effect of norfloxacin was associated to an enhanced mobilization of NADPH oxidase subunits p47phox and p67phox 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 O2•- and other reactive oxygen species.
Key Words: macrophages • reactive oxygen species • O2 • - • H2O2
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