title: Differential action of 3-hydroxyanthranilic acid on viability and activation of stimulated lymphocytes.
abstract: Lymphocytes proliferation after antigen-driven activation leads to an increase in cell count, which could last some week, until apoptosis mechanisms allow the homeostatic control of the system. During the first days of this stimulation, activated lymphocytes display high resistance to apoptosis and to most immunosuppressive drugs. According to the literature, few compounds have been described to kill recently activated cells, by inhibiting metabolic processes fundamental to proliferation. The aim of our work was to evaluate comparatively these different compounds, in order to identify the best strategy to kill cells that have undergone proliferation, while sparing the repertoire of resting cells. After preliminary experiments, 3-HAA and bortezomib were selected as the most suitable compounds for our purposes. The possible synergic effect of 3-HAA with bortezomib or with manganese ions was also assessed. 3-HAA was confirmed to be the most reliable pharmacologic approach to inhibit proliferation with acceptable toxicity on resting cells. While in the case of PHA stimulation 3-HAA led to death of most lymphocytes, only a minor percentage of cells were killed after allo-stimulation, suggesting that the effect is proportional to the percentage of stimulated lymphocytes. Manganese ions further enhanced this effect, while results with bortezomib seemed to be less consistent. These results deserve further investigations to develop new procedures for targeting activated cells with pharmacological approaches.
authors: Department of Medical Sciences, University of Trieste, Strada di Fiume 447, 34139 Trieste, Italy. elisa.piscianz@gmail.com
authors: Elisa
authors: E
authors: Piscianz
authors: Eva
authors: E
authors: Cuzzoni
authors: Sara
authors: S
authors: De Iudicibus
authors: Erica
authors: E
authors: Valencic
authors: Giuliana
authors: G
authors: Decorti
authors: Alberto
authors: A
authors: Tommasini
mesh_terms: D015095:3-Hydroxyanthranilic Acid / Q000633:toxicity*; D001897:Boronic Acids / Q000633:toxicity; D000069286:Bortezomib; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects*; D008345:Manganese / Q000633:toxicity; D011719:Pyrazines / Q000633:toxicity
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D015095:3-Hydroxyanthranilic Acid; D008345:Manganese; D000069286:Bortezomib