Abstract

Treatment of polymorphonuclear leukocytes (PMNs) with penicillamine has little effect on chemotaxis of the cells towards fMet-Leu-Phe. In the absence of fMet-Leu-Phe however, penicillamine has a strong effect on PMN locomotion. Penicillamine-induced enhancement of PMN migration is for an important part due to a chemokinetic effect, but there is also a chemotactic effect. Pretreatment of PMNs with membrane-impermeable sulfhydryl reagents has little effect on random locomotion, but completely abolishes the activating effect of penicillamine. This suggests that for the activating effect of penicillamine intact sulfhydryl groups on the outer surface of the PMN are required. Extracellular calcium is no absolute requirement for PMN migration, neither for random locomotion nor for the activating effect of penicillamine. Removal of intracellular Ca 2+ with membrane-penetrating Ca 2+-complexing agents strongly inhibit penicillamine-induced enhancement of PMN migration, underlining a role for intracellular calcium. Penicillamine causes an increase of cGMP level in PMNs. Though a simple relationship seems unlikely it is possible that the enhancement of PMN migration, and the increase of cGMP level by penicillamine are related processes.

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