Mistletoe viscotoxins increase natural killer cell-mediated cytotoxicity.
Mistletoe extracts have immunomodulatory activity. We show that nontoxic concentrations of Viscum album extracts increase natural killer (NK) cell-mediated killing of tumor cells but spare nontarget cells from NK lysis. The compounds responsible for this bioactivity were isolated from mistletoe and characterized. They have low molecular mass and are thermostable and protease-resistant. After complete purification by HPLC, they were identified by tandem MS as viscotoxins A1, A2 and A3 (VTA1, VTA2 and VTA3, respectively). Whereas micromolar concentrations of these viscotoxins are cytotoxic to the targets, the bioactivity with respect to NK lysis is within the nanomolar range and differs between viscotoxin isoforms: VTA1 (85 nm), VTA2 (18 nm) and VTA3 (8 nm). Microphysiometry and assays of cell killing indicate that, within such nontoxic concentrations, viscotoxins do not activate NK cells, but act on cell conjugates to increase the resulting lysis.
Tabiasco
Julie
J
Institut National de la Santé et de la Recherche Médicale U563 and Service de spectrométrie de masse de l' IFR 30, CHU Purpan, BP3028, Toulouse, France.
Pont
Frédéric
F
Fournié
Jean-Jacques
JJ
Vercellone
Alain
A
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D037102:Lectins / Q000494:pharmacology; D014784:Mistletoe; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins / Q000494:pharmacology; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D037102:Lectins; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; C488038:viscotoxin