Garenoxacin-induced increase of CD11b expression on human polymorphonuclear neutrophils does not affect phagocytosis and killing of Staphylococcus aureus.
Garenoxacin is considered to be the most active quinolone against Staphylococcus aureus. Quinolones are believed to alter the function of human polymorphonuclear leukocytes (PMN) and garenoxacin is known to be the only quinolone which alters the expression of the beta-chain (CD11b) of the complement receptor 3 (CR3) which is known to be important in the phagocytosis of S. aureus by PMN. Therefore, the effect of this altered CD11b expression on phagocytosis, oxidative burst, and killing of S. aureus was addressed and compared with that of standard quinolones. Phagocytosis and oxidative burst were determined by flow cytometry, and killing was measured by a colony-count method. Garenoxacin at therapeutic concentrations affected neither phagocytosis nor killing of Staphylococcus aureus NMS54. At supratherapeutic concentrations (1,500 mg/l) garenoxacin reduced and delayed phagocytosis like all other quinolones tested except norfloxacin. This decrease seems to be a result of inhibition of the oxidative burst of PMN and reduced CD11b expression at this supratherapeutic concentration. In conclusion, the alteration of CD11b expression of PMN caused by garenoxacin at 0.5, 5.0, and 100.0 mg/l is not considered to hamper the function of these first-line-defense phagocytes.
Grüger
Thomas
T
Biosafety Laboratory, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.
Reiners
Ana-Lena
AL
Schnitzler
Norbert
N
Brandenburg
Kerstin
K
Zündorf
Josef
J
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D039481:CD11b Antigen / Q000187:drug effects / Q000378:metabolism*; D015169:Colony Count, Microbial; D005434:Flow Cytometry; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D015363:Quinolones / Q000494:pharmacology; D016897:Respiratory Burst; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000302:isolation & purification; D015854:Up-Regulation
D000900:Anti-Bacterial Agents; D039481:CD11b Antigen; D024841:Fluoroquinolones; D015363:Quinolones; C419689:garenoxacin