EVIDENCE FOR BOTH OXYGEN AND NON-OXYGEN DEPENDENT MECHANISMS OF ANTIBODY SENSITIZED TARGET-CELL LYSIS BY HUMAN-MONOCYTES

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 56  (6) , 985-992
Abstract
The generation of reactive oxygen species (ROS) such as H2O2 or superoxide (O2) may play a role in monocyte antibody-dependent cytotoxicity (ADCC). ADCC was studied 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. Monocyte HMPS activity increased 2- to 3-fold 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 cell even though hypoxia markedly decreased monocyte HMPS activity. Monocytes from CGD patients had impaired lysis of RBC but lysed CEM cells normally. Protection by scavengers of ROS could not be demontrated. Monocyte ADCC involves 2 independent mechanisms: a nonoxidative mechanism active in the lysis of CEM cells, or an oxidative mechanism that may involve an unidentified ROS activated during ADCC toward RBC. The activation and possible interaction of these 2 mechanisms is determined by the nature of the target cell and sensitizing antibody.