Ciprofloxacin transport by chemoattractant-activated polymorphonuclear leukocytes: regulation by priming and protein kinase C.
At infection sites, polymorphonuclear leukocyte (PMN) function is enhanced ("primed") by granulocyte-macrophage colony-stimulating factor (GM-CSF) or lipopolysaccharide (LPS) and activated by formyl peptides. In this study, GM-CSF or LPS alone had no significant effects on PMN ciprofloxacin transport. Through a mechanism involving protein kinase C, activation by formyl-Met-Leu-Phe (fMLP) significantly decreased the K(m) of ciprofloxacin transport and enhanced ciprofloxacin accumulation. This effect was dramatically enhanced when PMNs were primed with GM-CSF or LPS prior to activation by fMLP.
D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000737:chemistry; D002614:Chelating Agents / Q000494:pharmacology; D002630:Chemotactic Factors / Q000378:metabolism / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000493:pharmacokinetics*; D019852:Diacylglycerol Kinase / Q000037:antagonists & inhibitors; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002614:Chelating Agents; D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002939:Ciprofloxacin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019852:Diacylglycerol Kinase; D011493:Protein Kinase C; D002118:Calcium