Naslov
The influence of multidrug transporter on macrolide uptake into RAW 264.7 murine macrophages

Autori
Munić, Vesna ; Kelnerić, Željko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
4th FEBS Advanced Lecture Course ATP-Binding Cassette (ABC) Proteins : From Multidrug Resistance to Genetic Disease : Abstract Book / - , 2001, 129-129

Skup
FEBS Advanced Lecture Course ATP-Binding Cassette (ABC) Proteins : From Multidrug Resistance to Genetic Disease (4 ; 2003)

Mjesto i datum
Gosau, Austrija, 01.03.2003. - 08.03.2003

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
multidrug transporter; macrolide; uptake; macrophage; RAW 264.7

Sažetak
All macrolides concentrate within phagocytic cells, with a mean intracellular to extracellular (I/E) concentration ratio higher than 10 whatever the type of phagocyte. In vitro studies have shown that polymorphonuclear leukocytes (PMN) achieve about ten times higher intracellular concentration of azithromycin than macrophages. Among macrolide antibiotics there are considerable differences in uptake and release kinetics (1) where azithromycin reaches several times higher intracellular concentration than erythromycin. Several authors reported the presence of MDR pumps in macrophages as well as the absence of similar pumps in PMNs. The aim of our research is to study the possible influence of multidrug transporter on intracellular accumulation of macrolides into RAW 264.7 murine macrophage cell line as well as to investigate the function of multidrug transporter in the same cells in the presence of azithromycin and erythromycin. Intracellular accumulation of macrolides was measured by microbiological method of diffusion in agar and the multidrug transporter activity was measured as daunorubicin uptake into cells by flow cytometer. Our results show that 3 microM cyclosporin A, a known inhibitor of MDR pump, induces an increase of daunorubicin uptake into RAW 264.7 cells by about 20%. Cytochalasin B (5-25 microg/mL), which is also known to interfere with MDR (2) induces dose dependant increase (15-25%) of daunorubicin uptake by RAW 264.7 cells. Moreover, cyclosporine A and cytochalasine B induced a 4 and 2.6 fold increase of azithromycin uptake into the same cell type. Studies on daunorubicin uptake into RAW 264.7 cells pre- and co-incubated with azithromycin or erythromycin (10 and 50 microM) show a correlation between the obtained intracellular concentration of a macrolide and the intensity of daunorubicin uptake with azithromycin displaying 10 and 40% increase depending on a dose, whereas the increase observed with erythromycin was 2 and 15%. The same trend but slightly lower increase was observed when the cells were just preincubated with macrolides. Our results indicate that azithromycin and erythromycin interfere with the activity of mammalian multidrug transporter and that the same transporter has a significant impact on macrolide accumulation in macrophages. References: 1. Miossec-Bartoli C, et al., 1999, Antimicrob Agents Chemother, 43, 2457 2. Zilfou JT, et al., 1995, Oncol Res, 7, 435

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA