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Updated: Sep 26, 2026
Imaging the Neutrophil Phagosome and Cytoplasm Using a Ratiometric pH Indicator
Published on: April 5, 2017
Clindamycin uptake by human neutrophils
Abstract:
An anaerobic environment limits the microbicidal capacity of polymorphonuclear neutrophils (PMNs). To augment PMN killing under these conditions, the characteristics and mechanisms of clindamycin uptake by human PMNs were studied. The peak intracellular concentration of clindamycin was approximately 40 times greater than the extracellular concentration. Clindamycin uptake was rapid, saturable, and temperature-dependent. Intracellular accumulation of the drug was inhibited in acid pH, and agents that collapsed the transmembrane pH gradients also inhibited uptake. Isolated PMN lysosomes also accumulated clindamycin against a large concentration gradient, and uptake was reduced by collapsing the translysosomal membrane pH gradient. The intracellular drug was fully bioactive. These studies demonstrate that clindamycin is rapidly accumulated by PMNs, that drug uptake is related to a pH gradient, and that clindamycin appears to be lysosomotropic.
Insights
Clindamycin is rapidly absorbed by human polymorphonuclear neutrophils (PMNs), enhancing their ability to kill microbes in anaerobic conditions. This uptake is pH-dependent, suggesting clindamycin is lysosomotropic.
Area of Science:
- Pharmacology
- Cell Biology
- Immunology
Background:
- Anaerobic environments impair the antimicrobial functions of polymorphonuclear neutrophils (PMNs).
- Enhancing PMN microbicidal capacity in low-oxygen conditions is crucial for treating certain infections.
Purpose of the Study:
- To investigate the uptake mechanisms of clindamycin by human PMNs.
- To understand how clindamycin concentration and activity are affected within PMNs.
Main Methods:
- Studied clindamycin uptake kinetics in human PMNs under varying conditions.
- Investigated the role of pH gradients and lysosomal accumulation.
- Assessed the bioactivity of intracellular clindamycin.
Main Results:
- Clindamycin achieved intracellular concentrations 40 times higher than extracellular levels.
- Uptake was rapid, saturable, temperature-dependent, and inhibited by acidic pH.
- PMN lysosomes actively accumulated clindamycin, indicating a lysosomotropic mechanism.
Conclusions:
- Clindamycin is efficiently accumulated by human PMNs via a pH-gradient-dependent, lysosomotropic mechanism.
- This enhanced intracellular concentration likely augments PMN microbicidal activity in anaerobic environments.
- Clindamycin demonstrates significant potential for boosting neutrophil function during anaerobic infections.
