β-Lactam Antibiotic Modulation of Murine Neutrophil Cytokinesis

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Abstract
Fourteen cephalosporins, 11 penicillins and 1 monobactam were evaluated for their in vitro modulation of murine neutrophil cytokinesis. As a result, the β-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↓): cloxacillin, cefotaxime, ceftazadime, cefuroxime, cephalothin, cephapirin, cephadine, nafcillin, piperacillin, ticarcillin, ampicillin, oxacillin, aztreonam; Group 3 (R↑D→): cephaloridine; Group 4 (R↑D↑): cefsulodin; Group 5 (R↑D↓): cefoperazone, cefoxitin, ceftriaxone, 6-amino-penicillanic acid; Group 6 (R↓D↓): cefadroxil, cefazolin, penicillin G, methicillin]. Trypan blue exclusion studies showed that inhibition of R and D by Group 6 β-lactam antibiotics is not due to overt cytotoxicity. β-lactam antibiotics inhibiting D also increased neutrophil adherence to plastic at a concentration of 1000 μM. Finally, the [Ca++] inhibitor chlorpromazine significantly abrogates β-lactam- and FMLP-directed migration at a test concentration of 1 μM.