Spontaneous programmed cell death (PCD) process of lymphocytes of FIV-infected cats: Pharmacological modulation in vitro

• Published in: International journal of immunopharmacology 1997-03, Vol.19 (3), p.167-179
• Main Authors: Guiot, Anne-Laure, Rigal, Dominique, Chappuis, Gilles
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; apoptosis; Apoptosis - drug effects; Apoptosis - immunology; Biological and medical sciences; cat; Cats; Cells, Cultured; Cycloheximide - pharmacology; Dactinomycin - pharmacology; Enterotoxins - pharmacology; FIV; Flow Cytometry; Immunodeficiency Virus, Feline - immunology; Interferon-gamma - pharmacology; Interleukin-1 - pharmacology; Interleukin-2 - pharmacology; Interleukin-6 - pharmacology; Ionomycin - pharmacology; Lentivirus Infections - blood; Lentivirus Infections - immunology; lymphocytes; Lymphocytes - immunology; Lymphocytes - metabolism; Medical sciences; Mitogens - pharmacology; Pharmacology. Drug treatments; PKC; propidium iodide; Protein Kinase C - antagonists & inhibitors; Protein Synthesis Inhibitors - pharmacology; Signal Transduction - physiology; Specific Pathogen-Free Organisms; Superantigens - pharmacology; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0192-0561; 1879-3495
• DOI: 10.1016/S0192-0561(97)00011-8

We previously reported that unstimulated lymphocytes in culture from FIV-infected cats undergo spontaneous apoptosis in vitro as indicated by internucleosomal DNA fragmentation and hypodiploid DNA content of nuclei. Unlike what is reported in HIV-infected individuals, we observed that cell death of cat lymphocytes was inhibited by activation. Spontaneous apoptosis was reduced by the addition of cat serum, interleukins [interleukin (IL)1, IL2, IL6 and interferon-γ (IFNγ)] and after activation by phorbol ester [phorbol myristyl acetate (PMA)], superantigens [staphylococcal enterotoxin B (SEB), staphylococcal enterotoxin A (SEA)], and to a lesser extent by mitogens such as Concanavalin A and pokeweed mitogen. In contrast, apoptosis of lymphocytes from FIV-infected, but not from control cats was increased in the presence of calcium ionophore (ionomycin). In this study, we studied the spontaneous programmed cell death (PCD)-inducing pathways, and the mechanisms of action of PMA, SEB and SEA. Spontaneous lymphocyte apoptosis of FIV-infected cats was inhibited by cycloheximide, ZnSO 4 and N-acetyl-cystein. The preventive effect of PMA was abolished by inhibitors of kinases (staurosporine, H7, genistein) and partially by actinomycin. The preventive effect of SEB and SEA was inhibited by actinomycin, but not by inhibitors of kinases. Calyculin, an inhibitor of phosphatase, had no effect either on spontaneous apoptosis, or on the action of PMA, SEB and SEA. Ionomycin-induced apoptosis was found sensitive to PMA and cytokines. In FIV-infected cats, these data suggest that the mature lymphocytes appear programmed to die by apoptosis, unless rescued by specific agents, such as protein kinase C activators or growth factors, and that spontaneous PCD seems to be dependent on de novo protein synthesis (see the effect of cycloheximide). The effects of PMA, SEB and SEA are probably mediated by de novo proteins which, for PMA, undergo a phosphorylation involving serine-threonine and/or tyrosine groups. Our data suggest a clear difference between lymphocytes from FIV-infected cats and lymphocytes from HIV-infected humans, with regard to their metabolic regulation.