Uptake of quinolones by in-vitro human monocyte derived macrophages

We have developed an in-vitro model of monocyte-derived macrophage (MDMO) t o compare fluoroquinolone uptake in monocytes and derived macrophages. Mono cyte-derived macrophages were obtained in-vitro by cultivating freshly isol ated monocytes for seven days in RPMI 1640 medium, containing foetal calf s erum and Rhu granulocyte-macrophage colony stimulating factor. Final suspen sions contained 95% viable cells and 63 % macrophages. Intramacrophagic acc umulation of ciprofloxacin, ofloxacin or sparfloxacin was measured at equil ibrium after 30-min incubation in the presence of 16-18 mug mL(-1) antibiot ic. The results revealed low intra-cellular accumulation of ofloxacin in MD MO (intracellular/extracellular ratio: IC/EC = 1.7), Ciprofloxacin and spar floxacin uptake was significantly higher. The IC/EC ratios were only slight ly increased in macrophages when compared with monocytes under the same exp erimental conditions. These results suggest that maturation of monocyte to macrophage has only a limited effect on basal quinolone uptake. Monocytic m aturation cannot explain the important differences between fluoroquinolone accumulation in monocytes and tissue macrophages. Cell activation may be a greater determinant.