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 < .05). Several observations suggested that this drug effect was the result of altered calcium metabolism: (1) exposure to verapamil decreased the uptake of 45Ca++ by PMNs subsequently exposed to the calcium ionophore A23187; (2) verapamil did not impair PMN function in the absence of extracellular calcium; and (3) 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 < .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 < .05). We conclude that PMNs exposed to pharmacological concentrations of calcium channel-blocking drugs exhibit a reduced capacity to kill bacteria.

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