TAILIEUCHUNG - Báo cáo Y học: Mistletoe viscotoxins increase natural killer cell-mediated cytotoxicity

Mistletoe extracts have immunomodulatory activity. We show that nontoxic concentrations ofViscumalbumextracts increase natural killer (NK) cell-mediated killing of tumor cells but spare nontarget cells from NK lysis. The com-pounds responsible for this bioactivity were isolated from mistletoe and characterized. They have low molecular mass and are thermostable and protease-resistant. | Eur. J. Biochem. 269 2591-2600 2002 FEBS 2002 doi Mistletoe viscotoxins increase natural killer cell-mediated cytotoxicity Julie Tabiasco1 Frederic Pont2 Jean-Jacques Fournie1 and Alain Vercellone1 1Institut National de la Sante et de la Recherche Médicale U563 and 2Service de spectrometrie de masse de I IFR 30 CHU Purpan BP3028 Toulouse France 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. Keywords mistletoe natural killer cells tumor cells viscotoxin Viscum album. Mistletoe preparations have been used for pharmacological purposes since ancient times 1 . These days industrially produced extracts from mistletoe are used in treatments of solid tumors 2-5 . It is thought that the molecular basis of the antitumoral activity of mistletoe lies in several distinct bioactivities. First its lectin content is responsible for direct toxicity to tumor cells 6-9 . Secondly the Viscum album rhamnogalacturonan oligosaccharide favors bridging of natural killer NK -tumor cell conjugates enhancing efficiency of killing 10-15 . Thirdly it has been found that the .

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