Saquinavir up-regulates telomerase activity in lymphocytes activated with monoclonal antibodies against CD3/CD28.
The present study describes the effect of the HIV protease inhibitor saquinavir on telomerase activity and interferon-gamma (IFN-gamma) production of nonadherent mononuclear cells (NA-MNC). Cells obtained from peripheral blood of healthy donors were exposed in vitro to a mixture of monoclonal antibodies against CD3 and CD28 membrane antigens in order to activate prevalently T cell subsets. Treatment with saquinavir was performed at the time of cell stimulation. Thereafter, NA-MNC were tested for telomerase activity (TRAP assay) and interferon-gamma production up to 7 days later. The results show that saquinavir up-regulates telomerase activity and IFN-gamma release in activated NA-MNC. These observations suggest that the anti-HIV effects of saquinavir could be accompanied by other immunopharmacological properties, influencing some aspects of the functional activity of immunocompetent cells. These include possible antagonistic effects against lymphocyte senescence, through telomerase activation, and a potentiating activity on the production of IFN-gamma following T cell activation.
Comandini
F A
FA
Department of Neuroscience, University of Rome Tor Vergata, Italy. franzese@med.uniroma2.it
Lombardi
A
A
Saponiero
A
A
Bonmassar
E
E
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002478:Cells, Cultured; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D019258:Saquinavir / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D019098:Telomerase / Q000378:metabolism*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D017320:HIV Protease Inhibitors; D007371:Interferon-gamma; D019098:Telomerase; D019258:Saquinavir