Effect of deuterium oxide on neutrophil oxidative metabolism, phagocytosis, and lysosomal enzyme release.

Abstract

We have previously shown that deuterium oxide (D2O) enhances the oxidation of methionine, a myeloperoxidase (MPO) -mediated reaction, by human neutrophils during phagocytosis. However, D2O has no effect on the oxidation of methionine by the purified MPO-H2O2-Cl- system. To explain this observation, we studied the effect of D2O on the oxidative metabolism, phagocytosis, and lysosomal enzyme release by human neutrophils. D2O stimulated the hexose monophosphate shunt (HMS) activity of resting neutrophils in a dose-response fashion. In the presence of latex particles or phorbol myristate acetate (PMA), D2O brought about an exaggerated stimulation of the HMS activity. This enhancement of the HMS activity by D2O was markedly reduced when neutrophils form two patients with X-linked chronic granulomatous disease (CGD) were used, either in the presence or absence of latex particles or PMA. Superoxide and H2O2 production by neutrophils in the presence of latex particles or PMA were also stimulated by D2O. In contrast, D2O inhibited the ingestion of latex particles. D2O enhanced the extracellular release of MPO, but not lactate dehydrogenase, by neutrophils only in the simultaneous presence of cytochalasin B and latex particles. The enhancement of HMS activity and MPO release by D2O was partially inhibited by colchicine. Our results suggest that enhancement of neutrophil oxidative metabolism by D2O may in part explain the stimulation of methionine oxidation by phagocytosing neutrophils.