Dual effect of phorbol myristate acetate on chemoattractant-induced locomotion of human neutrophils

Abstract

Phorbol myristate acetate (PMA) is a potent activator of Ca2+/phospholipid-dependent protein kinase (PKC) and was used to study the involvement of this kinase in human polymorphonuclear neutrophil (PMN) locomotion. Preincubation of PMNs with low concentrations of PMA (4 to 64 x 10(-11) M) had the following effects: (1) fMet-Leu-Phe-induced migration under agarose was increased when the chemoattractant was used at the suboptimal concentration of 10(-8)M and not at the optimal concentration of 10(-7)M; (2) no effect on spontaneous or serum- or LTB4- induced migration at either suboptimal or optimal concentrations; (3) PMA enhanced fMet-Leu-Phe-induced migration, increasing the speed of locomotion but not affecting shape changes induced by fMet-Leu-Phe; (4) the number of fMet-Leu-Phe-specific receptors expressed on the PMN membrane was not altered. Intermediate concentrations of PMA (1.6 to 4.0 x 10(-9) M) had no effect on PMN migration, whereas higher concentrations (4.0 to 16 x 10(-9) M) reduced both spontaneous and fMet-Leu-Phe-, serum-, or LTB4-induced migration in a dose-dependent manner. Effects observed with low concentrations of PMA were not associated with a translocation of cytosolic PKC even when preincubation with PMA was followed by fMet-Leu-Phe stimulation. In contrast, effects observed with higher concentrations of PMA paralleled the decrease in cytosolic PKC activity.