Differential induction of glucocorticoid-dependent apoptosis in murine lymphoid subpopulations in vivo following coexposure to lipopolysaccharide and vomitoxin (deoxynivalenol).
Lipopolysaccharide (LPS) and vomitoxin (VT) synergistically induce glucocorticoid- mediated apoptotic cell death in lymphoid tissues of the mouse. Based on the known effects of glucocorticoids, it was hypothesized that the combined exposure to LPS and VT targets immature lymphocyte populations. To test this hypothesis, we quantified the effects of VT and LPS on apoptosis induction in T lymphocyte subsets in thymus and B lymphocyte subsets in Peyer's patches and bone marrow. Flow cytometry revealed that a single dose of LPS (0.1 mg/kg body wt ip) together with VT (12.5 mg/kg body wt po) promoted apoptosis of immature (CD4(-)CD8(-), CD4(+)CD8(+)) and mature (CD4(-)CD8(+)) thymocytes at 12 h with a subsequent reduction of these populations being detectable at 24 h. RU 486, a glucocorticoid receptor antagonist, significantly abrogated apoptosis in CD4(-)CD8(-), CD4(+)CD8(+), and CD4(-)CD8(+) subsets and also prevented loss in cell numbers. In Peyer's patches, mature-B lymphocytes (B220(+)IgM(-)IgD(+)) underwent apoptosis and, in bone marrow, pro/pre-B lymphocytes (B220(+)IgM(-)IgD(-)) and mature-B lymphocytes (B220(+)IgM(-)IgD(+)) underwent apoptosis at 12 h after toxin co- exposure. RU 486 blocked LPS + VT-induced apoptosis of the aforementioned subsets in Peyer patches and bone marrow at 12 h. Taken together, these data suggest that LPS can interact with VT in mice to induce the glucocorticoid-driven apoptotic loss of immature thymocytes and cytotoxic T lymphocytes in thymus, mature-B lymphocytes in Peyer's patch, and pro/pre-B lymphocytes and mature-B lymphocytes in bone marrow in mice.
Islam
Zahidul
Z
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA.
King
Louis E
LE
Fraker
Pamela J
PJ
Pestka
James J
JJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D016516:CD4-CD8 Ratio; D003433:Crosses, Genetic; D005434:Flow Cytometry; D006727:Hormone Antagonists / Q000494:pharmacology; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014255:Trichothecenes / Q000276:immunology / Q000633:toxicity*
D006727:Hormone Antagonists; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D014255:Trichothecenes; D015735:Mifepristone; C007262:deoxynivalenol