Related Experiment Videos
beta-Lactam antibiotic modulation of murine neutrophil cytokinesis
M T Kenny1, F J Balistreri, H L Torney
1Marion Merrell Dow Research Institute, Indianapolis, Indiana 46268-0460.
Abstract:
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.
Insights
Beta-lactam antibiotics modulate neutrophil migration, with Group 6 antibiotics inhibiting random and directed migration without cytotoxicity. Chlorpromazine, a calcium inhibitor, also affects migration.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Neutrophil migration is crucial for immune response.
- Beta-lactam antibiotics are widely used antimicrobials.
- Understanding antibiotic effects on immune cells is important.
Purpose of the Study:
- To investigate the in vitro effects of various beta-lactam antibiotics on murine neutrophil migration.
- To classify beta-lactam antibiotics based on their modulatory effects on neutrophil chemotaxis.
- To assess the cytotoxicity of antibiotics affecting neutrophil migration.
Main Methods:
- In vitro evaluation of 14 cephalosporins, 11 penicillins, and 1 monobactam.
- Assessing random (R) and FMLP-directed (D) neutrophil migration.
- Trypan blue exclusion assays for cytotoxicity.
- Neutrophil adherence assays.
- Testing the effect of calcium channel blocker chlorpromazine.
Main Results:
- Beta-lactam antibiotics were categorized into 6 groups based on their differential effects on R and D migration.
- Group 6 antibiotics (cefadroxil, cefazolin, penicillin G, methicillin) inhibited both R and D migration without causing cytotoxicity.
- Antibiotics inhibiting directed migration also increased neutrophil adherence.
- Chlorpromazine significantly inhibited both beta-lactam and FMLP-directed migration.
Conclusions:
- Beta-lactam antibiotics exhibit diverse modulatory effects on neutrophil migration.
- Inhibition of neutrophil migration by certain beta-lactams is not due to direct cell toxicity.
- Calcium signaling pathways may play a role in beta-lactam-mediated modulation of neutrophil function.