Role of Activated Macrophage Superoxide Anions and Hydrogen Peroxide in Immune Suppression

  • J. Terrell Hoffeld
  • Zvi Metzger
  • Joost J. Oppenheim


Bacterial cells and their products are among the most potent inducers of macrophage activation (2). In turn, activated macrophages can be both stimulators and suppressors of lymphocyte functions. Dr. Oppenheim has already detailed what we believe to be the stimulatory macrophage mechanisms (22). The suppression of lymphocyte function in vitro and/or in vivo has been attributed to a growing list of macrophage-derived materials (Table I) (1). Despite the longevity of most of the macrophage products which are suppressive, it is difficult to reproduce, with culture supernatants, the full extent of suppression observed in the original cultures. This suggested that the suppressive activity of activated macrophages might be mediated by short-lived products and/or required close macrophage-lymphocyte contact. Since the complement fractions and prostaglandins are relatively labile and difficult to isolate from supernatants of lymphocyte cultures suppressed by activated macrophages, they remained reasonable candidates as mediators of the suppression. An additional group of short-lived, potentially-suppressive substances released by activated macrophages is the group of oxygen metabolites, including the superoxide anion and hydrogen peroxide. Since these bactericidal molecules had not been previously considered in the context of iymphocytostasis, we have investigated their involvement in several in vitro models of the immune response. In this paper, we will first consider the mechanism of the production of superoxide by macrophages and the mode of its toxic action on other cells. We will then present data implicating superoxide as having a damping effect on the normal antibody response, in vitro. Finally, we will show that the overwhelming suppressive effect of macrophages activated by exposure to Corynebacterium parvum (C. parvum; Propionibacterium acnis) cells is mediated by both hydrogen peroxide and prostaglandins, together.


Antibody Response Peritoneal Cell Plaque Form Cell Reduce Nicotinamide Adenine Dinucleotide Hexose Monophosphate Shunt 
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Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • J. Terrell Hoffeld
    • 1
  • Zvi Metzger
    • 1
  • Joost J. Oppenheim
    • 1
  1. 1.Laboratory of Microbiology and Immunology Cellular Immunology SectionNIH, NIDRBethesdaUSA

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