Modulation of polymorphonuclear leukocyte function by cetiedil.
Cetiedil citrate monohydrate inhibits sickling of red cells and aggregation of platelets. We assessed its ability to attenuate polymorphonuclear leukocyte (PMN) function. PMN aggregation in response to 2 X 10(-7) M formyl-met-leu-phe (FMLP) was inhibited in a dose-dependent fashion by cetiedil concentrations ranging from 60 to 250 microM. Additionally, 125 microM cetiedil inhibited PMN aggregation in response to 2 X 10(-7) M FMLP, 20 ng/ml phorbol myristate acetate (PMA), and 1 X 10(-6) M A23187 by 69% +/- 18%, 72% +/- 20%, and 65% +/- 4%, respectively. Inhibition of FMLP-induced aggregation was provided by only 5 min of incubation of the drug with the cells and was partially reversible. Cell viability was unaffected by exposure of PMN to the drug. Correspondingly, 125 microM cetiedil prevented the translocation of calcium from the PMN membrane as assessed by chlorotetracycline fluorescence. Paralleling the effect of the drug on PMN aggregation, 125 microM cetiedil inhibited release of superoxide by 55% and decreased the number of available 3H-FMLP receptors. However, its effect on release of the primary granule constituent, myeloperoxidase, was minimal (4.5% inhibition), while the effect on release of the specific granule product, lactoferrin (27% inhibition), was modest. These studies indicate that cetiedil affects PMN aggregation and superoxide release to a much greater extent than PMN degranulation. Thus, cetiedil may have potential uses in modulating inflammatory response in vivo.
D001381:Azepines / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D003572:Cytochalasins / Q000494:pharmacology; D006801:Humans; D007781:Lactoferrin / Q000097:blood; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects*; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D009195:Peroxidase / Q000097:blood; D013481:Superoxides / Q000378:metabolism
D001381:Azepines; D003572:Cytochalasins; D009842:Oligopeptides; D013481:Superoxides; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; C006955:cetiedil; D009195:Peroxidase; D007781:Lactoferrin; D002118:Calcium