Role of the myeloperoxidase-H2O2-halide system in concanavalin A-induced tumor cell killing by human neutrophils

R. A. Clark, S. J. Klebanoff

Research output: Contribution to journalArticle

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Abstract

Human blood neutrophils in the presence of the lectin, concanavalin A, exhibited potent cytotoxic activity against murine lymphoma cells (LSTRA) as assessed by 51Cr release from labeled target cells. Tumor cell killing was rapid, with significant 51Cr release observed at 30 min and maximal release at 2 hr. Cytotoxicity showed a linear relationship to the log of the effector cell:target cell ratio, with significant killing detected at ratios as low as one neutrophil to 20 LSTRA cells. Under the conditions employed, human blood mononuclear leukocytes (lymphocytes plus monocytes) were not effective killer cells. Cytotoxicity required halides (chloride, iodide) for maximal activity and was markedly reduced by agents that inhibit heme enzymes (azide, cyanide) or degrade H2O2 (catalase). Neutrophils deficient in myeloperoxidase or the respiratory burst had impaired cytotoxic activity, and these defects were corrected by the addition of purified myeloperoxidase or an H2O2-generating enzyme system, respectively. Concanavalin A also initiated protein iodination by neutrophils, a process that requires myeloperoxidase and H2O2. Both cytotoxicity and iodination were inhibited in a dose-related fashion by α-methyl-D-mannoside, a carbohydrate that blocks concanavalin A binding to mammalian cell membranes. These data demonstrate that concanavalin A-induced neutrophil-mediated tumor cell cytotoxicity occurs as a consequence of lectin-binding to the effector cell. Furthermore, this surface stimulation results in the secretion of the lysosomal enzyme, myeloperoxidase, and the metabolic product H2O2. These agents combine with extracellular halides to form a system that is cytotoxic to mammalian tumor cells.

Original languageEnglish (US)
Pages (from-to)2605-2610
Number of pages6
JournalJournal of Immunology
Volume122
Issue number6
StatePublished - Jan 1 1979
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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