Monocyte Antibody-dependent Cytotoxicity Research Articles

Increased antibody-dependent cytotoxicity mediated by purified monocytes in Hodgkin's disease

Monocyte antibody-dependent cytotoxicity was studied in 19 patients with Hodgkin's disease and 14 normal controls. This function was investigated after isolation of the monocytes by means of a modified elutriation technique. Direct sizing and counting of the cells present in the effluent enabled individual adjustment during each separation procedure. The absolute monocyte count in the peripheral blood of patients with Hodgkin's disease was higher ( P < 0.002) than in normal controls. Nearly 90% pure monocyte suspensions, representing 82% of all elutriated monocytes, were obtained. The elutriation characteristics of the monocytes in both groups were essentially the same, irrespective of marked interindividual differences. Kill of antibody-coated chicken red blood cells was measured by DNA flow cytometry. In comparison to normal controls, a significantly increased ( P < 0.0004), stage-independent, monocyte antibody-dependent cytotoxicity was found in patients with Hodgkin's disease. The percentage of kill in symptomatic patients tended to be higher than in the asymptomatic group; no correlation was found with the absolute number of circulating monocytes.

Evidence for Both Oxygen and Non-Oxygen Dependent Mechanisms of Antibody Sensitized Target Cell Lysis by Human Monocytes

Recent studies suggest that the generation of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) or superoxide (O2-) may play a role in monocyte antibody-dependent cytotoxicity (ADCC). We studied ADCC by normal human monocytes, and monocytes from chronic granulomatous disease (CGD) patients, cells unable to generate ROS, toward anti-D sensitized human red cells (RBC) and an antibody sensitized lymphoblastoid cell line (CEM) by 51Cr release. The effects of hypoxia, scavengers of ROS, and the activity of the hexose monophosphate shunt pathway (HMPS) were examined. We found that monocyte HMPS activity increased two to threefold during ADCC toward RBC but was unchanged during ADCC toward CEM cells. Hypoxia decreased lysis of RBC targets by 80% but did not affect lysis of CEM cells even though hypoxia markedly decreased monocyte HMPS activity. Monocytes from CGD patients had impaired lysis of RBC but lysed CEM cells normally. We could not, however, demonstrate protection by scavengers of ROS. We conclude that monocyte ADCC involves two independent mechanisms: a nonoxidative mechanism active in the lysis of CEM cells, and an oxidative mechanism that may involve an unidentified ROS activated during ADCC toward RBC. The activation and possible interaction of these two mechanisms is determined by the nature of the target cell and sensitizing antibody.

Evidence for both oxygen and non-oxygen dependent mechanisms of antibody sensitized target cell lysis by human monocytes

Recent studies suggest that the generation of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) or superoxide (O2-) may play a role in monocyte antibody-dependent cytotoxicity (ADCC). We studied ADCC by normal human monocytes, and monocytes from chronic granulomatous disease (CGD) patients, cells unable to generate ROS, toward anti-D sensitized human red cells (RBC) and an antibody sensitized lymphoblastoid cell line (CEM) by 51Cr release. The effects of hypoxia, scavengers of ROS, and the activity of the hexose monophosphate shunt pathway (HMPS) were examined. We found that monocyte HMPS activity increased two to threefold during ADCC toward RBC but was unchanged during ADCC toward CEM cells. Hypoxia decreased lysis of RBC targets by 80% but did not affect lysis of CEM cells even though hypoxia markedly decreased monocyte HMPS activity. Monocytes from CGD patients had impaired lysis of RBC but lysed CEM cells normally. We could not, however, demonstrate protection by scavengers of ROS. We conclude that monocyte ADCC involves two independent mechanisms: a nonoxidative mechanism active in the lysis of CEM cells, and an oxidative mechanism that may involve an unidentified ROS activated during ADCC toward RBC. The activation and possible interaction of these two mechanisms is determined by the nature of the target cell and sensitizing antibody.