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 c1indamycin uptake by human PMNs were studied. The peak intracellular concentration of c1indamycin was ∼40 times greater than the extracellular concentration. Clindamycin uptake was rapid, saturable, and temperaturedependent. 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 c1indamycin 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 c1indamycin is rapidly accumulated by PMNs, that drug uptake is related to a pH gradient, and that clindamycin appears to be lysosomotropic.