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Augmentation of spontaneous macrophage-mediated cytolysis by eosinophil peroxidase.

Abstract
Eosinophil peroxidase (EPO), a cationic protein purified from horse blood, adhered to four different types of tumor cells, markedly potentiating their lysis by preformed or enzymatically generated H(2)0(2) (up to 76-fold, as assayed in serum-containing tissue culture medium without supplemental halide). Similarly, compared with uncoated tumor cells, EPO-coated tumor cells were up to 32 times more sensitive to lysis when incubated with macrophages or granulocytes whose respiratory burst was triggered by PMA. However, EPO-coated tumor cells were also readily lysed by bacillus Calmette- Guerin-activated macrophages in the absence of exogenous triggering agents. This spontaneous cytolysis was rapid (50 percent at 2 h) and potent (50 percent lysis at macrophage/tumor cell ratios of 1.5 to 4.6), and was observed with both a peroxide-sensitive tumor (TLX9) and a peroxide-resistant tumor (NK lymphoma). Under the conditions used, neither EPO alone nor macrophages alone were spontaneously cytolytic. Neither EPO nor EPO-coated tumor cells triggered a detectable increment in H(2)0(2) release from macrophages. Nonetheless, spontaneous macrophage-mediated cytolysis of EPO- coated tumor cells was completely inhibitable by catalase (50 percent inhibition, 23 U/ml), although not by heated catalase, indicating a requirement for H(2)0(2). Cytolysis was also completely inhibitable by azide (50 percent inhibition, 2.6 X 10 -5 M), indicating a requirement for enzymatic activity of EPO. Thus, a cytophilic peroxidase from eosinophils and H(2)0(2) spontaneously released from activated macrophages interacted synergistically in a physiologic medium to destroy tumor cells.
AuthorsC F Nathan, S J Klebanoff
JournalThe Journal of experimental medicine (J Exp Med) Vol. 155 Issue 5 Pg. 1291-308 (May 01 1982) ISSN: 0022-1007 [Print] United States
PMID6802924 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Bromides
  • Chlorides
  • Iodides
  • Hydrogen Peroxide
  • Eosinophil Peroxidase
  • Peroxidases
  • Tetradecanoylphorbol Acetate
Topics
  • Animals
  • Bromides (pharmacology)
  • Chlorides (pharmacology)
  • Cytotoxicity, Immunologic (drug effects)
  • Eosinophil Peroxidase
  • Eosinophils (enzymology)
  • Female
  • Horses
  • Hydrogen Peroxide (pharmacology)
  • Iodides (pharmacology)
  • Lymphoma (immunology)
  • Macrophage Activation
  • Macrophages (metabolism)
  • Mast-Cell Sarcoma (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Peroxidases (pharmacology)
  • Tetradecanoylphorbol Acetate (pharmacology)
  • Time Factors

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