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Characterization of Minocycline Transport by Human Neutrophils
Author(s) -
Walters John D.
Publication year - 2006
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2006.060096
Subject(s) - minocycline , doxycycline , extracellular , chemistry , pharmacology , tetracycline , antibiotics , intracellular , efflux , microbiology and biotechnology , biochemistry , medicine , biology
Background: Tetracyclines are used in periodontal therapy as antimicrobial agents and as inhibitors of matrix metalloproteinases. Neutrophils appear to accumulate minocycline and other tetracyclines through a mechanism that has not been fully characterized. Methods: The transport of minocycline and other tetracyclines by isolated human neutrophils was characterized by measuring the increase in cell‐associated fluorescence. Results : Quiescent neutrophils took up minocycline through a saturable, concentrative, sodium‐dependent mechanism with a Michaelis constant (K m ) of 153 μg/ml (501 μM) and a maximal velocity of 240 ng/minute/10 6 cells. The efficiency of minocycline transport was not influenced significantly by a two‐unit variation in extracellular pH and was not enhanced upon cell activation with phorbol myristate acetate. Neutrophil incubation in medium containing 10 μg/ml minocycline, doxycycline, or tetracycline yielded steady‐state intracellular/extracellular concentration ratios of ∼64.0, 7.5, or 1.8, respectively. The dilution of extracellular minocycline or doxycycline triggered efflux from cells loaded with these antibiotics. Minocycline transport was competitively inhibited by the organic cations carnitine, diphenhydramine, and verapamil, but penicillin and other organic anions failed to produce inhibition. Conclusion: Transport of tetracyclines by neutrophils could potentially enhance the effectiveness of these agents in periodontal therapy by enhancing or sustaining their therapeutic levels at inflammatory sites and by enhancing the killing of phagocytosed bacterial pathogens.