Immunomodulation by neutrophil myeloperoxidase and hydrogen peroxide: Differential susceptibility of human lymphocyte functions

To coexistence of activated polymorphonuclear leukocytes and lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. To test this hypothesis, we examined the effects of neutrophil myeloperoxidase and H₂O₂ on lymphocytes. Human peripheral blood mononuclear leukocytes were exposed to myeloperoxidase, and H₂O₂-generating system (glucose + glucose oxidase), and a halide, and were then tested for functional activities. Natural killer activity against K562 cells, lymphocyte proliferation in response to mitogens, and generation of immunoglobulin-secreting cells were all susceptible to oxidative injury by myeloperoxidase and H₂O₂. The degree as well as the mechanism of suppression was dependent on the glucose oxidase concentration (i.e., the rate of H₂O₂ delivery). At low H₂O₂ flux, myeloperoxidase was essential for induction of lymphocyte suppression; as the rate of H₂O₂ generation increased, suppression became myeloperoxidase-independent and was mediated by H₂O₂ alone. Various lymphocyte functions were differentially susceptible to oxidative injury by myeloperoxidase and H₂O₂. The proliferative response to pokeweed mitogen was the least sensitive, whereas antibody formation was the most sensitive. Proliferative responses to concanavalin A and phytohemagglutinin as well as natural killer activity displayed intermediates degrees of susceptibility. In all assays, lymphocyte viability was >90%. Removal of monocytes from mononuclear leukocytes by adherence to glass increased susceptibility of lymphocytes to oxidative injury. Monocytes in proportions within the range present in peripheral blood mononuclear leukocytes protected lymphocytes functions against oxidative injury by myeloperoxidase and H₂O₂. This study demonstrates a differential susceptibility of various immune functions to oxidative injury by the neutrophil products myeloperoxidase and H₂O₂, and shows, in addition, that monocytes can modulate these interactions.