Bone marrow stromal-B cell interactions in polycyclic aromatic hydrocarbon-induced pro/pre-B cell apoptosis
Bone marrow stromal-B cell interactions in polycyclic aromatic hydrocarbon-induced pro/pre-B cell apoptosis
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DOI：
10.1093/toxsci/kfg239
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发表时间：
2003-12-01
影响因子：
3.8
通讯作者：
Sherr, DH
中科院分区：
文献类型：
--
作者：
Allan, LL;Mann, KK;Sherr, DH
环境中的多环芳烃 (PAH) 和相关卤代烃在多种系统中都具有免疫毒性。在 B 淋巴细胞生成模型系统中，PAH 暴露迅速诱导 CD43(-) pre-13 和 CD43(+) pro/pre-B 细胞凋亡。 7,12-二甲基苯并[a]蒽 (DMBA) 诱导的细胞凋亡依赖于 AhR(+) 骨髓基质细胞，并且可能涉及基质细胞内的 DMBA 代谢。然而，尚不清楚经 PAH 处理的基质细胞是否释放可能直接诱导 B 细胞死亡的游离代谢物或可溶性因子，或者效应死亡信号是否通过基质细胞-B 细胞接触传递。在这里，我们证明，DMBA 处理的骨髓基质细胞的上清液含有能够诱导与基质细胞共培养的 pro/pre-B 细胞凋亡的活性。当基质细胞与 DMBA 和α-萘黄酮 (α-NF)、芳基碳氢化合物受体 (AhR) 和细胞色素 P-450 抑制剂共处理时，不会产生此活性 (1)，(2) 大于或等于 50 kDa，(3) 对胰蛋白酶和热敏感，(4) 依赖于 AhR(+) 基质细胞，后者反过来将效应子死亡信号传递给 pro/pre-13细胞。结果 (1) 反对可溶性基质细胞衍生的细胞因子作为 PAH 诱导的 pro/pre-13 细胞死亡效应物的作用，(2) 排除了游离代谢物直接作用于 AhR-pro/pre-B 细胞靶标的可能性，(3) 表明基质的阐述。细胞具有相对稳定的 DMBA 代谢物-蛋白质复合物，能够作用于其他基质。细胞在一定距离内。总的来说，这些研究表明，虽然基质细胞产物（例如代谢物-蛋白质复合物）可能影响远处基质细胞的功能，但基质细胞向骨髓 B 细胞传递的效应死亡信号是由细胞与细胞接触介导的。
Environmental polycyclic aromatic hydrocarbons (PAH) and related halogenated hydrocarbons are immunotoxic in a variety of systems. In a model system of B lymphopoiesis, PAH exposure rapidly induces apoptosis in CD43(-) pre-13 and CD43(+) pro/pre-B cells. Apoptosis induction by 7,12-dimethylbenzo[a]anthracene (DMBA) is dependent upon AhR(+) bone marrow stromal cells and likely involves DMBA metabolism within the stromal cell. However, it is not known if PAH-treated stromal cells release free metabolites or soluble factors that may directly induce B cell death or if the effector death signal is delivered by stromal cell-B cell contact. Here, we demonstrate that, supernatants from DMBA-treated bone marrow stromal cells contain an activity capable of inducing apoptosis in pro/pre-B cells cocultured with stromal cells. This activity (1) is not produced when stromal cells are cotreated with DMBA and a-naphthoflavone (alpha-NF), an aryl hydrocarbon receptor (AhR) and cytochrome P-450 inhibitor, (2) is greater than or equal to 50 kDa, (3) is trypsin and heat sensitive, and (4) is dependent on AhR(+) stromal cells, which in turn deliver the effector death signal to pro/pre-13 cells. The results (1) argue against a role for a soluble, stromal cell-derived cytokine as the effector of PAH-induced pro/pre-13 cell death, (2) exclude the possibility of a free metabolite acting directly on AhR-pro/pre-B cell targets, and (3) suggest the elaboration by stromal. cells of a relatively stable, DMBA metabolite-protein complex capable of acting on other stromal. cells at some distance. Collectively, these studies suggest that, while stromal cell products, e.g., metabolite-protein complexes, may affect the function of distant stromal cells, the effector death signal delivered by stromal cells to bone marrow B cells is mediated by cell-cell contact.