Characteristics and mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes

Authors
Citation
Wl. Hand et Dl. Hand, Characteristics and mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes, INT J ANT A, 18(5), 2001, pp. 419-425
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Microbiology
Journal title
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
ISSN journal
0924-8579 → ACNP
Volume
18
Issue
5
Year of publication
2001
Pages
419 - 425
Database
ISI
SICI code
0924-8579(200111)18:5<419:CAMOAA>2.0.ZU;2-7
Abstract
Azithromycin achieves prolonged, high tissue concentrations in spite of low serum levels and obviously must be active at tissue sites of infection to be effective. These unique features prompted us to evaluate the interaction s of azithromycin and human polymorphonuclear leukocytes (PMN). Uptake of r adiolabeled antibiotic by PMN was determined by a velocity-gradient centrif ugation technique and expressed as the ratio of cellular to extracellular d rug concentration (CIE). Azithromycin was massively accumulated by human PM N (C/E = 387.2 at 2 h). Uptake was not influenced by inhibitors of cellular metabolism, but phagocytosis slightly inhibited the entry of azithromycin into PMN. After removal of extracellular drug, the release (efflux) of azit hromycin from PMN was extremely slow. Agents which neutralize lysosomal pH, preventing protonation and trapping of azithromycin, markedly increased an tibiotic efflux. Active concentration and prolonged retention of azithromyc in by phagocytic cells should allow delivery and subsequent release of accu mulated drug at sites of infection. (C) 2001 Elsevier Science B.V. and Inte rnational Society of Chemotherapy. All rights reserved.