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Regulation of ciprofloxacin uptake in human promyelocytic leukemia cells and polymorphonuclear leukocytes
Author(s) -
Loo Kwor C.,
Cario Anthony C.,
Zhang Fanjie,
Walters John D.
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.61.5.619
Subject(s) - chelerythrine , protein kinase c , biology , downregulation and upregulation , ciprofloxacin , n formylmethionine leucyl phenylalanine , phorbol , granulocyte , pharmacology , microbiology and biotechnology , kinase , neutrophile , immunology , biochemistry , in vitro , antibiotics , gene
Polymorphonuclear leukocytes (PMNs) actively internalize ciprofloxacin, a capability that can enhance killing of intracellular bacteria and facilitate delivery of the antimicrobial agent to infection sites by migrating PMNs. In this study we investigated mechanisms for upregulation of this process. Activation with N ‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP; 100 nM) enhanced PMN ciprofloxacin uptake by 50% ( P < 0.05). Phorbol myristate acetate (PMA; 10 nM) enhanced uptake by at least 36‐fold, mainly by stimulating an increase in the V max of the ciprofloxacin transporter. This effect of PMA was inhibited by antagonists of protein kinase C (H7 and chelerythrine) and the mitogen‐activated protein kinase cascade downstream (PD 098059). Under resting and PMA‐activated conditions, ciprofloxacin uptake by immature human promyelocytic leukemia (HL‐60) cells was much lower than in PMNs. However, when HL‐60 cells were induced to mature into PMN‐like cells, their ciprofloxacin uptake activity increased markedly. These findings implicate a role for protein kinase C in upregulation of the ciprofloxacin transporter and suggest that myeloid cells acquire an enhanced ability to take up ciprofloxacin as they mature to end‐stage PMNs. J. Leukoc. Biol. 61: 619–623; 1997.