title: Differential modulation of apoptosis and necrosis by antioxidants in immunosuppressed human lymphocytes.
abstract: In the present study, we explored whether mitogenic stimulation of dexamethasone (DXM)- and cyclosporine A (CsA)-immunosuppressed peripheral blood lymphocytes (PBML) induced apoptosis or necrosis and their relation with the production of reactive oxygen intermediates. Our results indicate that both phenomena can occur in these cells and that antioxidants such as N-acetyl cysteine (NAC) and ascorbic acid (AA) can modulate them. However, DXM-induced apoptosis was only partially inhibited by NAC and AA, suggesting that DXM-treated PBMC had an additional apoptotic pathway independent of ROIs. Furthermore, we observed that the inhibition of apoptosis by antioxidants correlated with an increased cell proliferation, suggesting that the immunomodulation of both DXM and CsA may be related to induction of apoptosis. The ability to differentially modulate apoptosis and necrosis by antioxidants opens new possibilities in the management of immunosuppressive therapy, since the inhibition of necrosis may avoid inflammation and the tissue damage associated with immunosuppressors.
authors.affiliation: Grupo de Inmunología Celular e Inmunogenética, Labioratorio Central de Investigaciones, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rojas
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Rugeles
authors.forename: Diana Patricia
authors.initials: DP
authors.lastname: Gil
authors.forename: Pablo
authors.initials: P
authors.lastname: Patiño
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001205:Ascorbic Acid / Q000494:pharmacology; D016572:Cyclosporine / Q000009:adverse effects / Q000276:immunology; D003907:Dexamethasone / Q000009:adverse effects / Q000276:immunology; D005938:Glucocorticoids / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000276:immunology*; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009336:Necrosis; D010835:Phytohemagglutinins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D000111:Acetylcysteine; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000975:Antioxidants; D001205:Ascorbic Acid; D016572:Cyclosporine; D003907:Dexamethasone; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D007770:L-Lactate Dehydrogenase; D037181:Lectins, C-Type; D010835:Phytohemagglutinins; D013481:Superoxides; D000099192:CD69 Antigens