Cytoprotection against neutrophil-delivered oxidant attack by antibiotics.
In the present study we have investigated the effect of six antibiotics (penicillin G, ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin) on the neutrophil cytolytic activity by using a system constituted of phorbol-12-myristate-13-acetate-triggered neutrophils and 51Cr-labelled lymphoblastoid Daudi target cells. The results demonstrate that five of these drugs (ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin) are capable of inhibiting the neutrophil cytolytic activity by inactivating the hypochlorous acid (HOCl) generated extracellularly by the myeloperoxidase pathway and crucial to the target cell lysis. Penicillin G had no effect on neutrophil-mediated cytolysis. Thus, these data demonstrate that ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin lower the neutrophil-mediated target cell damage by a HOCl-scavenging mechanism, suggesting a possible cytoprotective role for these drugs during infections.
Ottonello
L
L
Department of Internal Medicine, University of Genova Medical School, Italy.
Dallegri
F
F
Dapino
P
P
Pastorino
G
G
Sacchetti
C
C
D000667:Ampicillin / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D003603:Cytotoxins / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010400:Penicillin G / Q000494:pharmacology*; D010878:Piperacillin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003603:Cytotoxins; D006997:Hypochlorous Acid; D000667:Ampicillin; D002442:Ceftazidime; D013755:Tetradecanoylphorbol Acetate; D010400:Penicillin G; D010878:Piperacillin