Faropenem enhances superoxide anion production by human neutrophils in vitro.
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.
Sato
K
K
First Department of Internal Medicine, Gunma University School of Medicine, Showa, Maebashi, Japan. satoken@akagi.sb.gunma-u.ac.jp
Sato
N
N
Shimizu
H
H
Tsutiya
T
T
Takahashi
H
H
Kakizaki
S
S
Takayama
H
H
Takagi
H
H
Mori
M
M
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
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