Influence of drugs that block calcium channels on the microbicidal function of human neutrophils

Abstract

The central role of calcium ions in cell physiology prompted us to examine the hypothesis that pharmacological concentrations of calcium channel-blocking drugs might affect human neutrophil (PMN) functions. The capacity of PMNs suspended in verapamil hydrochloride for killing Pseudomonas aeruginosa during two hour incubations was significantly impaired (P less than .05). Several observations suggested that this drug effect was the result of altered calcium metabolism: exposure to verapamil decreased the uptake of 45Ca++ by PMNs subsequently exposed to the calcium ionophore A23187; verapamil did not impair PMN function in the absence of extracellular calcium; and the addition of A23187 concomitantly with (but not following) verapamil prevented PMN dysfunction. In addition, nifedipine, a structurally dissimilar calcium channel-blocking drug, also impaired the bactericidal activity of PMNs against Pseudomonas aeruginosa (P less than .02). Further studies revealed that treatment with verapamil did not affect PMN phagocytosis, but significantly impaired the PMN respiratory burst (as shown by superoxide anion generation assay; P less than .05). We conclude that PMNs exposed to pharmacological concentrations of calcium channel-blocking drugs exhibit a reduced capacity to kill bacteria.