Human monocyte to macrophage differentiation in vitro: characterization and mechanisms of the increased antibody-dependent cytotoxicity associated with differentiation

Abstract

Human monocyte-to-macrophage differentiation in vitro is associated with marked enhancement in the capacity to bind and lyse antibody-opsonized red blood cells (rbc). We previously demonstrated that this was due in part to an increased number of Fc receptors. The current study further characterized the mechanism of this enhanced macrophage as antibody-dependent cellular cytotoxicity (ADCC). We observed that 1) macrophages but not monocytes lysed "innocent bystander" rbc as well as opsonized rbc; 2) macrophages exhibited an increased hexose monophosphate shunt activity compared to monocytes; 3) macrophage produced H2O2 but not OH.; and 4) macrophage lyses of opsonized rbc were 80% O2 dependent. We conclude that human monocyte-to-macrophage maturation in vitro is associated with an enhanced O2-dependent cytotoxic mechanism normally present in monocytes. The enhanced H2O2 production noted in macrophages may reflect an increased generation of several other reactive oxygen species in these cells. One of these oxygen radicals may be the mediator of the enhanced macrophage cytotoxicity and of the "innocent bystander" phenomenon observed.