Uptake of antibiotics by human polymorphonuclear leukocyte cytoplasts
- Veterans Administration Medical Center (Atlanta), Decatur, GA (USA)
Enucleated human polymorphonuclear leukocytes (PMN cytoplasts), which have no nuclei and only a few granules, retain many of the functions of intact neutrophils. To better define the mechanisms and intracellular sites of antimicrobial agent accumulation in human neutrophils, we studied the antibiotic uptake process in PMN cytoplasts. Entry of eight radiolabeled antibiotics into PMN cytoplasts was determined by means of a velocity gradient centrifugation technique. Uptakes of these antibiotics by cytoplasts were compared with our findings in intact PMN. Penicillin entered both intact PMN and cytoplasts poorly. Metronidazole achieved a concentration in cytoplasts (and PMN) equal to or somewhat less than the extracellular concentration. Chloramphenicol, a lipid-soluble drug, and trimethoprim were concentrated three- to fourfold by cytoplasts. An unusual finding was that trimethroprim, unlike other tested antibiotics, was accumulated by cytoplasts more readily at 25 degrees C than at 37 degrees C. After an initial rapid association with cytoplasts, cell-associated imipenem declined progressively with time. Clindamycin and two macrolide antibiotics (roxithromycin, erythromycin) were concentrated 7- to 14-fold by cytoplasts. This indicates that cytoplasmic granules are not essential for accumulation of these drugs. Adenosine inhibited cytoplast uptake of clindamycin, which enters intact phagocytic cells by the membrane nucleoside transport system. Roxithromycin uptake by cytoplasts was inhibited by phagocytosis, which may reduce the number of cell membrane sites available for the transport of macrolides. These studies have added to our understanding of uptake mechanisms for antibiotics which are highly concentrated in phagocytes.
- OSTI ID:
- 6510843
- Journal Information:
- Antimicrobial Agents and Chemotherapy; (USA), Vol. 34:6; ISSN 0066-4804
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTIBIOTICS
MEMBRANE TRANSPORT
CARBON ISOTOPES
CELL MEMBRANES
CELL NUCLEI
CENTRIFUGATION
LEUKOCYTES
MAN
METABOLISM
TRACER TECHNIQUES
UPTAKE
ANIMALS
ANTI-INFECTIVE AGENTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CONSTITUENTS
DRUGS
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MATERIALS
MEMBRANES
PRIMATES
SEPARATION PROCESSES
VERTEBRATES
550501* - Metabolism- Tracer Techniques