Lymphocyte stem cell alterations following perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Lymphocyte stem cell alterations following perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
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发表时间：
1989
影响因子：
3.6
通讯作者：
J. S. Fine;T. Gasiewicz;A. Silverstone
中科院分区：
文献类型：
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作者：
J. S. Fine;T. Gasiewicz;A. Silverstone
实验动物围产期暴露于环境污染物2，3，7，8-四氯二苯并-对二恶英(TCDD)会导致胸腺萎缩和细胞免疫抑制，这种抑制比成人暴露所引起的更严重和持续，这表明参与免疫系统成熟的事件对TCDD特别敏感。我们在这里报道，围产期接触TCDD会导致胎儿和新生儿中淋巴细胞干细胞数量的变化，这是淋巴细胞干细胞特异性酶末端脱氧核苷酸转移酶(TDT)显著降低的证据。在妊娠第14天单次注射TCDD(10微克/公斤体重)后，孕18天胎肝淋巴样细胞TDT生物合成和TDT特异性mRNA的合成减少了50%以上。出生后第18天，新生儿骨髓中TDT合成的减少幅度更大。相比之下，胸腺TDT合成在围产期对每个细胞的影响相对较小，尽管由于胸腺广泛萎缩，合成TDT的胸腺细胞的实际数量减少了。这些效应发生在TCDD/mg胸腺浓度为1-31fg时。流式细胞仪分析胸腺细胞表面标志物的表达，发现Lyt-2+L3T4+胸腺细胞的百分比在出生后第18天和出生后第4天略有下降，但到出生后第11天这种变化不再明显，此时骨髓TDT生物合成受到最大的抑制。这些结果表明，TCDD在围产期引起的胸腺萎缩可能部分是由于对前胸腺细胞的影响。
Perinatal exposure of experimental animals to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to thymic atrophy and a suppression of cell-mediated immunity that is more severe and persistent than that caused by adult exposure, suggesting that events involved in the maturation of the immune system are particularly sensitive to TCDD. We report here that perinatal TCDD exposure produces an alteration in the lymphocyte stem cell population in the fetus and neonate, as evidenced by a significant reduction in the lymphocyte stem cell-specific enzyme terminal deoxynucleotidyl transferase (TdT). After maternal treatment with a single dose of TCDD (10 micrograms/kg of body weight) on gestational day (gd) 14, TdT biosynthesis and TdT-specific mRNA were reduced more than 50% in fetal liver lymphoid cells on gd 18. An even more extensive reduction was seen in neonatal bone marrow through postnatal day 18. In contrast, thymic TdT synthesis appeared to be relatively unaffected on a per cell basis by perinatal TCDD exposure, although the actual number of TdT-synthesizing thymocytes was diminished due to extensive thymic atrophy. These effects occurred at concentrations of 1-31 fg of TCDD/mg of thymus. Flow cytometric analysis of thymocyte surface marker expression revealed a slight decrease in the percentage of Lyt-2+L3T4+ thymocytes on gd 18 and postnatal day 4. This alteration was no longer apparent by postnatal day 11, when marrow TdT biosynthesis was most suppressed. These results suggest that TCDD-induced thymic atrophy during the perinatal period may be due, in part, to an effect on the prothymocyte.