title: Faropenem enhances superoxide anion production by human neutrophils in vitro.
abstract: Neutrophils are important cellular components in the defence against infections and many studies in vitro have shown that some antibiotics affect neutrophil function. We examined the effect of faropenem, a new oral penem antibiotic on neutrophil killing function by determining the generation of superoxide anion in vitro. The production of superoxide anion was measured by chemiluminescence amplified by a Cypridina luciferin analogue in the presence of N-formyl-Met-Leu-Phe (fMLP). Faropenem significantly enhanced chemiluminescence in a dose-dependent manner. The effect of faropenem was maximal at 5 min of incubation time and continued for at least 30 min. The effect of faropenem was also observed when neutrophils were stimulated by a calcium ionophore (ionomycin), while the effect of faropenem did not change in the presence of 12-O-tetra-decanoylphorbolmyristate acetate. Cytosol Ca2+ concentration ([Ca2+]i) monitored with Fura-2 increased in response to fMLP, however, faropenem did not influence the response of [Ca2+]i to fMLP. Our results suggest that faropenem enhanced the generation of superoxide anion by neutrophils, probably at the site where cytosol Ca2+ regulates NADPH oxidase. Faropenem might be potentially advantageous in the treatment of infections because a synergic interaction of antibodies and cytocidal neutrophils is necessary for the early eradication of the pathogenic bacteria.
authors.affiliation: First Department of Internal Medicine, Gunma University School of Medicine, Showa, Maebashi, Japan. satoken@akagi.sb.gunma-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.forename: T
authors.initials: T
authors.lastname: Tsutiya
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Kakizaki
authors.forename: H
authors.initials: H
authors.lastname: Takayama
authors.forename: H
authors.initials: H
authors.lastname: Takagi
authors.forename: M
authors.initials: M
authors.lastname: Mori
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D049454:Firefly Luciferin / Q000737:chemistry; D006801:Humans; D015759:Ionomycin / Q000737:chemistry; D007769:Lactams; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000737:chemistry; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D007769:Lactams; D047090:beta-Lactams; D013481:Superoxides; D015759:Ionomycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D049454:Firefly Luciferin; C107057:fropenem; D002118:Calcium