Evidence for both oxygen and non-oxygen dependent mechanisms of antibody
sensitized target cell lysis by human monocytes
DK Klassen and AL Sagone
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.
Volume 56,
Issue 6,
pp. 985-992,
12/01/1980
Copyright © 1980 by The American Society of Hematology
