Induction of PreB cell apoptosis by 7,12-dimethylbenz[a]anthracene in long-term primary murine bone marrow cultures.
Induction of PreB cell apoptosis by 7,12-dimethylbenz[a]anthracene in long-term primary murine bone marrow cultures.
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DOI：
10.1006/taap.1997.8263
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发表时间：
1997-12
影响因子：
3.8
通讯作者：
Koichi Yamaguchi;Raymond A. Matulka;Alexander M. Shneider;Paul Toselli;A. Trombino;Shi Yang;
中科院分区：
文献类型：
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作者：
Koichi Yamaguchi;Raymond A. Matulka;Alexander M. Shneider;Paul Toselli;A. Trombino;Shi Yang;
大量研究表明，多环芳烃(PAH)通过改变B细胞和T细胞的功能来抑制免疫。相对较少的研究评估了这些常见环境化学物质对未成熟淋巴细胞的影响。本研究采用长期原代骨髓培养的方法，研究了PAH和芳香烃受体(AhR)激动剂7，12-二甲基苯并[a]菲(DMBA)对未成熟B淋巴细胞的作用。在这个系统中，未成熟的Preb细胞维持在骨髓基质细胞提供的支持性微环境中。结果表明：(1)原代培养的骨髓细胞暴露于DMBA可导致Preb细胞通过凋亡而死亡；(2)低剂量DMBA(-gt；或=10(-8)M)可诱导Preb细胞凋亡；(3)原位杂交、RT-PCR和免疫印迹检测显示，长期培养的骨髓基质细胞表达AhR mRNA和蛋白，而免疫印迹法检测不表达AhR蛋白；(4)免疫组织化学检测新鲜分离的未分离的骨髓B细胞表达AhR蛋白；(5)竞争性的AhR抑制剂和细胞色素P450拮抗剂α-萘黄酮能完全阻断DMBA诱导的原代骨髓培养的Preb细胞的凋亡；(6)DMBA或苯并[a]芘体内注射导致骨髓细胞凋亡，与聚集在基质元素周围的造血细胞死亡一致。这些结果提示程序性细胞死亡是DMBA介导的免疫抑制的一种机制，并提示Preb细胞死亡受到与AhR+骨髓基质细胞局部相互作用的影响。
Numerous studies demonstrate that polycyclic aromatic hydrocarbons (PAH) suppress immunity by modifying the function of both B and T cells. Relatively few studies have assessed the effects of these common environmental chemicals on immature lymphocytes. In the present study, long-term primary bone marrow cultures were employed to investigate the effects of a prototypic PAH and aryl hydrocarbon receptor (AhR) agonist, 7,12-dimethylbenz[a]anthracene (DMBA), on immature B lymphocytes. In this system, immature preB cells are maintained in a supportive microenvironment provided by bone marrow stromal cells. Results presented here demonstrate that (1) exposure of primary bone marrow cultures to DMBA results in preB cell death by apoptosis; (2) notably low doses of DMBA (> or = 10(-8) M) induce preB cell apoptosis; (3) in long-term cultures, bone marrow stromal cells, but not preB cells, express AhR mRNA and protein as determined by in situ hybridization, RT-PCR, and immunoblotting; (4) freshly isolated unfractionated bone marrow cells, but not purified bone marrow B cells, express AhR protein as assessed by immunohistochemistry; (5) alpha-naphthoflavone, a competitive AhR inhibitor and cytochrome P450 antagonist, completely blocks DMBA-induced preB cell apoptosis in primary bone marrow cultures; and (6) DMBA or benzo[a]pyrene injection in vivo results in bone marrow cell apoptosis consistent with the death of hematopoietic cells clustered around stromal elements. The results implicate programmed cell death as a mechanism underlying DMBA-mediated immunosuppression and suggest that preB cell death is influenced by local interactions with AhR+ bone marrow stromal cells.