Oxidative Mechanisms of Monocyte-Mediated Cytotoxicity

Human monocytes stimulated with phorbol myristate acetate were able to rapidly destroy autologous erythrocyte targets. Monocyte-mediated cytotoxicity was related to phorbol myristate acetate concentration and monocyte number. Purified preparations of lymphocytes were incapable of mediating erythrocy...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1980-01, Vol.77 (1), p.584-587
Main Authors: Weiss, Stephen J., LoBuglio, Albert F., Kessler, Howard B.
Format: Article
Language:English
Subjects:
Catalase - metabolism
Cyanides
Cytolysis
Cytotoxicity
Cytotoxicity, Immunologic - drug effects
Enzymes
Erythrocytes - immunology
Free Radicals
Humans
Lymphocytes
Monocytes
Monocytes - immunology
Myristates
Neutrophils
Neutrophils - immunology
Peroxides - metabolism
Phorbols
Superoxide Dismutase - metabolism
Superoxides
Superoxides - metabolism
Tetradecanoylphorbol Acetate - pharmacology
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Summary:Human monocytes stimulated with phorbol myristate acetate were able to rapidly destroy autologous erythrocyte targets. Monocyte-mediated cytotoxicity was related to phorbol myristate acetate concentration and monocyte number. Purified preparations of lymphocytes were incapable of mediating erythrocyte lysis in this system. The ability of phorbol myristate acetate-stimulated monocytes to lyse erythrocyte targets was markedly impaired by catalase or superoxide dismutase but not by heat-inactivated enzymes or albumin. Despite a simultaneous requirement for superoxide anion and hydrogen peroxide in the cytotoxic event, a variety of hydroxyl radical and singlet oxygen scavengers did not effect cytolysis. However, tryptophan significantly inhibited cytotoxicity. The myeloperoxidase inhibitor cyanide enhanced erythrocyte destruction, whereas azide reduced it modestly. The inability of cyanide to reduce cytotoxicity coupled with the protective effect of superoxide dismutase suggests that cytotoxicity is independent of the classic myeloperoxidase system. We conclude that monocytes, stimulated with phorbol myristate acetate, generate superoxide anion and hydrogen peroxide, which together play an integral role in this cytotoxic mechanism.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.77.1.584