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

Abstract

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.

Hypoxia‐activated ADCC‐enhanced humanized anti‐CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity

“…Compared with the action under normoxia, these two Abs induced little CDC and ADCP and the triggered ADCC was diminished under hypoxia (Figures 4I–L and S8I–L). Such hypoxia‐impaired immunological effects are in line with previous observations that other Abs decrease the ADCC, ADCP, and CDC in tumors 50–54 . The underlying mechanisms are unclear, but may be associated with hypoxia‐related downregulation of immune function 51,55,56 .…”

“…Such hypoxia‐impaired immunological effects are in line with previous observations that other Abs decrease the ADCC, ADCP, and CDC in tumors. 50 , 51 , 52 , 53 , 54 The underlying mechanisms are unclear, but may be associated with hypoxia‐related downregulation of immune function. 51 , 55 , 56 The decreased but not disappeared ADCC induced by HAP18 Ab is attributed to enhanced ADCC characteristic of HcHAb18 Ab (Figure 2 ).…”

Phorbol myristate acetate-induced modulation of antibody-dependent cellular cytotoxicity by human polymorphonuclear leukocytes

“…Clark and JKlebanoff (5) and Hafeman and Lucas (10) reported that ROS is responsible for the ADCC of polymorphonuclear leukocytes (PMNs) against mammalian tumor cells. However, other workers have suggested that mechanisms other than ROS generation from the phagocytic cells may be responsible for ADCC activity (4,8,14,16,17).…”