Fluoroquinolone transport by human monocytes: characterization and comparison to other cells of myeloid lineage.
Human monocytes transport and accumulate ciprofloxacin and other fluoroquinolones. Although little is known about the mechanisms of transport, we expected monocytes to be similar to other cells of myeloid lineage. In the present study, monocyte fluoroquinolone transport was characterized and compared to the corresponding transport pathways of human polymorphonuclear leukocytes (PMNs) and HL-60 cells. Ciprofloxacin transport by monocytes was saturable, temperature dependent, sodium independent, and relatively insensitive to pH. Quiescent monocytes transported ciprofloxacin with a K(m) of 171 microg/ml and a V(max) of 32.7 ng/min/10(6) cells. Adenine competitively inhibited ciprofloxacin transport by quiescent monocytes (K(i) = 3.8 mM), but nucleosides had no significant inhibitory effect. In all of these respects, transport by monocytes was similar to that observed for quiescent PMNs and immature HL-60 cells. Unlike PMNs, however, monocytes and immature HL-60 cells did not exhibit dramatically enhanced ciprofloxacin transport when activated by phorbol myristate acetate (PMA). Consistent with this finding, HL-60 cells committed to granulocytic differentiation exhibited a significant component of PMA-inducible ciprofloxacin transport activity, while HL-60 cells committed to monocytic differentiation did not. In PMNs, the PMA-inducible component of transport appeared to be mobilized from a granule compartment, since its activity could be modulated by agents that enhance or inhibit stimulated degranulation. Thus, quiescent monocytes, PMNs, and HL-60 cells take up ciprofloxacin via similar energy-dependent transport mechanisms. Unlike granulocytes, monocytes do not express a second, higher-affinity pathway for ciprofloxacin accumulation when they are activated by PMA.
Bounds
S J
SJ
Section of Periodontology, College of Dentistry, College of Medicine, The Ohio State University Health Sciences Center, Columbus, Ohio, USA.
Nakkula
R
R
Walters
J D
JD
D000225:Adenine / Q000378:metabolism; D000890:Anti-Infective Agents / Q000378:metabolism*; D001693:Biological Transport, Active; D001854:Bone Marrow Cells / Q000378:metabolism; D002939:Ciprofloxacin / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D007781:Lactoferrin / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D012964:Sodium / Q000502:physiology
D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D012964:Sodium; D007781:Lactoferrin; D000225:Adenine