Differential action of 3-hydroxyanthranilic acid on viability and activation of stimulated lymphocytes

Elisa Piscianz, Eva Cuzzoni, Sara De Iudicibus, Erica Valencic, Giuliana Decorti, Alberto Tommasini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2242-2245
Number of pages4
JournalInternational Immunopharmacology
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 2011

Keywords

  • 3-hydroxyanthranilic acid
  • Activated lymphocytes
  • Bortezomib
  • Mixed Lymphocyte Reaction
  • Proliferation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

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