Characteristics of the metabolic response of human monocytes to red cells sensitized with anti-D alloantibodies.

In these studies we have characterized the metabolism of the HMPS pathway of PBMs and PMNs from normal persons during interaction with human red cells sensitized with anti-D alloantibody. This was correlated with ADCC as determined by the 51Cr release assay. In this system, the lysis by PBMs of RBCs sensitized with anti-D alloantibodies was mediated by both monocytes and lymphocytes, although the activity of the monocytes was greater. Monocytes, but not lymphocytes, has a burst in HMPS activity during interaction with anti-D-sensitized RBCs. This could be detected with T:E ratios similar to those which caused 51Cr release from the target. Oxygen was required for optimal lysis of antibody-coated RBCs by monocytes, but ADCC was not totally impaired under hypoxic conditions, suggesting that mononuclear cells may have at least two mechanisms for accomplishing ADCC-one that is oxygen-dependent and another that does not involve oxygen radicals. ADCC under aerobic conditions was accompanied by a burst in HMPS activity. In the absence of oxygen there was a 60% reduction in ADCC and no stimulation of the HMPS. However, results of studies for detection of oxygen radicals using standard scavengers during ADCC were negative. In contrast to monocytes, PMNs did not mediate significant ADCC in similar T:E ratios and did not have a metabolic burst when incubated with anti-D-sensitized RBCs. This appears to relate to the low activity of PMNs compared to monocytes in the lysis of RBCs sensitized with anti-D antibody.