Reduction in Peripheral Lymphocytes and Thymus Atrophy Induced by Organotin Compounds In Vivo

Abstract

ABSTRACT. To clarify the involvement of apoptosis in the immunotoxicity of organotin compounds, we examined the induction of apoptosis in the peripheral lymphocytes and thymus of mice treated with triphenyltin (TPT), tributyltin (TBT) or dexamethasone (Dex). Application of TPT or TBT and Dex resulted in a transient reduction in peripheral lymphocytes at 3 to 6 hr, and thymus atrophy was observed at 6 and 24 hr after administration. Lymphocyte subpopulation analysis showed that TPT and TBT induced a greater reduction in B cells than in T cells. The maximum levels of organotin in the blood were about 450 ng TPT/ml in the TPT-treated mice, and 170 ng TBT/ml in the TBT-treated mice. When the isolated peripheral lymphocytes were incubated with the organotins at 500 ng/ml, TPT and TBT induced necrosis in over 70% of cells, while both organotins caused lower percentages of apoptosis as well as necrosis after 3 hr at 100 ng/ml. In the thymus, although in vivo treatment of mice with Dex caused apoptosis, neither apoptotic nor necrotic thymocytes were observed in the TPT-and TBT-treated mice, indicating that the thymus atrophy might be caused by the antiproliferative effects of these organotin compounds. Thus, our results did not support the idea that apoptosis played a decisive part in the immunotoxicity of the organotin compounds in vivo.KEY WORDS: organotin compounds, peripheral lymphocytes, thymus atrophy.

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“…We have done so with splenic lymphocytes from naive B6 donors, because both the baseline granulopoiesis defect and the defective granulopoietic response to dexamethasone were observed in the absence of allergic sensitization. The number (10 7 ) of lymphocytes for transfer into individual mice was defined on the basis of similar reconstitution studies [ 23 ]. To define whether elimination of a particular lymphocyte subpopulation defined by standard surface markers (CD4/CD8) prevented reconstitution of the dexamethasone response, 10 7 total lymphocytes purified from spleen were submitted to alternative depletion protocols with marker-specific microbeads, and the depleted cells in the column effluent, corresponding to the number of cells negative for the selection marker present in the original lymphocyte sample, were injected.…”

“…Samples were therefore collected 72 h after transfer. Where indicated, bone-marrow, peripheral blood from the abdominal vena cava, spleens, and whole thymuses were collected, for enumeration of cells or determination of relative weight of the thymus (mg/g body weight) [ 21 , 23 ]. Bone-marrow collected from both femurs of each mouse in 5 mL RPMI1640 medium/1% FBS with a 22-gauge needle and kept on ice was used for total and differential counts and cell culture (see below).…”

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“…Organotins also induce PPARg-dependent apoptosis in lymphoma cells or lymphocytes in thymus. Lymphocyte subpopulation analysis has shown that both TPT and TBT induced a greater reduction in B cells than in T cells (Ueno et al, 2009).…”