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Penetration of macrolides into human polymorphonuclear leucocytes
1Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
The Journal of Antimicrobial Chemotherapy
|November 1, 1989
Summary
This study investigated macrolide antibiotic transport into human white blood cells. Results show high intracellular concentrations, suggesting active transport mechanisms influenced by cell conditions and phagocytosis.
Area of Science:
- Pharmacology
- Cell Biology
- Infectious Diseases
Background:
- Macrolide antibiotics are crucial for treating bacterial infections.
- Understanding their cellular uptake is vital for optimizing therapeutic efficacy.
- Polymorphonuclear leucocytes play a key role in immune defense against pathogens.
Purpose of the Study:
- To quantify the transport of five macrolide antibiotics into human polymorphonuclear leucocytes.
- To investigate the mechanisms and factors influencing macrolide antibiotic cellular accumulation.
- To assess how phagocytosis of bacteria affects macrolide antibiotic uptake.
Main Methods:
- Utilized 14C-labelled macrolide antibiotics (erythromycin, josamycin, clarithromycin, rokitamycin, roxithromycin).
- Measured intracellular/extracellular concentration ratios (transport ratios) in human polymorphonuclear leucocytes.
- Assessed the impact of environmental factors (temperature, pH) and metabolic inhibitors (formaldehyde, KF, NaCN, ouabain, DNP, adenosine, puromycin) on transport.
- Examined macrolide transport during phagocytosis of Legionella pneumophila, Staphylococcus aureus, and opsonized zymosan.
Main Results:
- High transport ratios (6.6–30.5) were observed for all five macrolides, indicating significant intracellular accumulation.
- Transport was reduced by low temperature, low pH, formaldehyde, and specific metabolic inhibitors, suggesting an active, energy-dependent process.
- Adenosine and puromycin significantly inhibited macrolide transport, except for erythromycin.
- Phagocytosis of Legionella pneumophila decreased macrolide transport, while phagocytosis of Staphylococcus aureus or zymosan generally increased it (except for roxithromycin).
Conclusions:
- Human polymorphonuclear leucocytes actively accumulate macrolide antibiotics.
- The transport mechanisms are influenced by cellular energy status and specific molecular interactions.
- Phagocytic activity can modulate macrolide antibiotic uptake, with varying effects depending on the pathogen involved.