Flow cytometric analysis of the effects of in vitro exposure to vomitoxin (deoxynivalenol) on apoptosis in murine T, B and IgA+ cells.
The immunotoxic effects of the trichothecene vomitoxin (VT or deoxynivalenol) and other trichothecenes may be mediated by direct interaction with lymphocytes. In this study, flow cytometric cell cycle analysis was used in conjunction with phenotypic staining by specific fluorescein isothiocyanate antibody conjugates to assess the in vitro effects of VT and another protein synthesis inhibitor, cycloheximide (CHX), on apoptosis in specific T- and B-cell subsets within thymus, spleen and Peyer's patch (PP) cultures. Both VT and CHX markedly inhibited T-cell apoptosis in dexamethasone (9 alpha-fluoro-16 alpha-methylprednisolone)-induced (DEX+) cells isolated from thymus, spleen and PP. Apoptosis-associated internucleosomal DNA fragmentation in whole thymus cell lysates as measured by gel electrophoresis was qualitatively consistent with flow cytometry among the various treatment groups. VT and CHX induced apoptosis in untreated (DEX-) T, B. and IgA+ cells from spleen and PP, whereas the effects of VT and CHX on DEX-induced apoptosis in B and IgA+ cells from these sources were negligible. These findings indicate that VT could either inhibit or enhance programmed cell death in a concentration-dependent manner and that this was dependent on lymphocyte subset, tissue source and glucocorticoid induction.
Pestka
J J
JJ
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824.
Yan
D
D
King
L E
LE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000633:toxicity; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D007070:Immunoglobulin A / Q000032:analysis; D051379:Mice; D010581:Peyer's Patches / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014255:Trichothecenes / Q000633:toxicity*
D007070:Immunoglobulin A; D014255:Trichothecenes; D003907:Dexamethasone; D003513:Cycloheximide; D016650:Fluorescein-5-isothiocyanate; C007262:deoxynivalenol