Regulation of Glycogen Metabolism in Polymorphonuclear Leukocytes

Abstract When polymorphonuclear leukocytes were incubated in medium without glucose for 1 hour, glycogen content declined at an essentially constant rate, whereas with 10 mm glucose there was no net change in glycogen during this period. Intracellular glucose 6-phosphate rose during the first 10 min of incubation in both media, but the rate was more than doubled in the presence of glucose. At the same time, ATP levels tended to be higher and those of AMP and orthophosphate lower when glucose was present in the medium than in its absence. The concentration of cyclic AMP (adenosine 3',5'-monophosphate) decreased by about 45% in 5 min whether or not glucose was present. The percentage of glycogen synthetase in the glucose-6-P-independent form was slightly but significantly higher in cells incubated for 10 min with glucose, whereas the total activity was not influenced by the presence of glucose in the medium. Glucose caused a rapid (5 min) decrease in phosphorylase activity which remained depressed for about 30 min and then rose gradually reaching the control level in 60 min. 2-Deoxyglucose procuced a greater depression which was maintained for 60 min. When cells were incubated with latex particles (in the absence of glucose), the rate of glycogen breakdown was accelerated during the first 15 min, but afterward (when phagocytosis was completed), approximated that of the resting cells. During phagocytosis, there was a delay in the accumulation of glucose-6-P, but levels of ATP, ADP, AMP, Pi, cyclic AMP, phosphorylase, and glycogen synthetase (glucose-6-P independent and total) were not significantly different from those in resting cells during the first 15 min. Theophylline, 1 mm, decreased leukocyte phosphorylase activity by 36% in 5 min without altering levels of cyclic AMP or the activation state of glycogen synthetase. Prostaglandin E1 in the presence of theophylline increased phosphorylase activity and cyclic AMP levels and decreased the percentage of glucose-6-P-independent glycogen synthetase. The effect of prostaglandin E1 on phosphorylase activity was observed whether or not either glucose or theophylline, or both, was present in the medium. In cells incubated with 20 mm NaF plus theophylline, levels of phosphorylase and cyclic AMP were increased. In the absence of theophylline, NaF decreased the percentage of glucose-6-P-independent glycogen synthetase and had no measurable effect on cyclic AMP levels. Neither NaF nor prostaglandin E1 significantly increased net glycogen breakdown in 1 hour of incubation. Although the leukocyte phosphorylase and glycogen synthetase activities can be influenced by agents acting through the cyclic AMP system, exogenous glucose modifies the activity of these enzymes without changing cyclic AMP levels. The marked acceleration in glycogen breakdown associated with phagocytosis is probably secondary to increased utilization of glucose-6-P and is not accompanied by changes in these enzymes or in cyclic AMP concentrations. Some data on the effects of glucose-6-P, Mg++, ATP, and orthophosphate on leukocyte glycogen synthetase activity are reported.