beta-Lactam antibiotic modulation of murine neutrophil cytokinesis.
Fourteen cephalosporins, 11 penicillins and 1 monobactam were evaluated for their in vitro modulation of murine neutrophil cytokinesis. As a result, the beta-lactam antibiotics were placed into 6 groups based on their effect on random (R) and FMLP-directed (D) migration [Group 1 (no effect): cephalosporin C; Group 2 (R-->D decreases): cloxacillin, cefotaxime, ceftazadime, cefuroxime, cephalothin, cephapirin, cephadine, nafcillin, piperacillin, ticarcillin, ampicillin, oxacillin, aztreonam; Group 3 (R increases D-->): cephaloridine; Group 4 (R increases D increases): cefsulodin; Group 5 (R increases D decreases): cefoperazone, cefoxitin, ceftriaxone, 6-amino-penicillanic acid; Group 6 (R decreases D decreases): cefadroxil, cefazolin, penicillin G, methicillin]. Trypan blue exclusion studies showed that inhibition of R and D by Group 6 beta-lactam antibiotics is not due to overt cytotoxicity. beta-lactam antibiotics inhibiting D also increased neutrophil adherence to plastic at a concentration of 1000 microM. Finally, the [Ca++] inhibitor chlorpromazine significantly abrogates beta-lactam- and FMLP-directed migration at a test concentration of 1 microM.
Kenny
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Marion Merrell Dow Research Institute, Indianapolis, Indiana 46268-0460.
Balistreri
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Torney
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D002746:Chlorpromazine