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 language | English |
|---|---|
| Pages (from-to) | 2242-2245 |
| Number of pages | 4 |
| Journal | International Immunopharmacology |
| Volume | 11 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2011 |
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Keywords
- 3-hydroxyanthranilic acid
- Activated lymphocytes
- Bortezomib
- Mixed Lymphocyte Reaction
- Proliferation
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Pharmacology
Cite this
Differential action of 3-hydroxyanthranilic acid on viability and activation of stimulated lymphocytes. / Piscianz, Elisa; Cuzzoni, Eva; De Iudicibus, Sara; Valencic, Erica; Decorti, Giuliana; Tommasini, Alberto.
In: International Immunopharmacology, Vol. 11, No. 12, 12.2011, p. 2242-2245.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential action of 3-hydroxyanthranilic acid on viability and activation of stimulated lymphocytes
AU - Piscianz, Elisa
AU - Cuzzoni, Eva
AU - De Iudicibus, Sara
AU - Valencic, Erica
AU - Decorti, Giuliana
AU - Tommasini, Alberto
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - 3-hydroxyanthranilic acid
KW - Activated lymphocytes
KW - Bortezomib
KW - Mixed Lymphocyte Reaction
KW - Proliferation
UR - http://www.scopus.com/inward/record.url?scp=81855185551&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=81855185551&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2011.09.009
DO - 10.1016/j.intimp.2011.09.009
M3 - Article
C2 - 21979495
AN - SCOPUS:81855185551
VL - 11
SP - 2242
EP - 2245
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 12
ER -