Cyp1b1-mediated suppression of lymphoid progenitors in bone marrow by polycyclic aromatic hydrocarbons coordinately impacts spleen and thymus: a selective role for the Ah Receptor.
Cyp1b1-mediated suppression of lymphoid progenitors in bone marrow by polycyclic aromatic hydrocarbons coordinately impacts spleen and thymus: a selective role for the Ah Receptor.
复制标题
Cyp1b1 介导的多环芳烃对骨髓中淋巴祖细胞的抑制协同影响脾脏和胸腺：Ah 受体的选择性作用。
DOI：
10.1002/prp2.245
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发表时间：
2016-08
影响因子：
2.6
通讯作者：
Jefcoate CR
中科院分区：
文献类型：
--
作者：
Larsen MC;N'Jai AU;Alexander DL;Rondelli CM;Forsberg EC;Czuprynski CJ;Jefcoate CR
Bone marrow (BM) hematopoietic stem cells differentiate to common lymphoid progenitors (CLP) that emigrate to the thymus to form T cells or differentiate into immature B cells that then migrate to the spleen for maturation. Rapid in vivo suppression of BM progenitor cells by a single oral or intraperitoneal dose of 7,12‐dimethylbenz(a)anthracene (DMBA) subsequently decreased mature lymphoid populations in BM, spleen, and thymus. These suppressions depended on BM CYP1B1, but not on aryl hydrocarbon receptor (AhR) activity. Suppression of pre‐B colony formation at 6 h, correlated with subsequent decreases in mature BM, spleen, and thymus populations (48–168 h). Thymus T‐cell ratios were unaffected, suggesting low local toxicity. DMBA treatment suppressed progenitor cells 24‐h post treatment in wild type (WT), AhRb mice, but not in Cyp1b1‐ko mice. The stem cell populations were sustained. Benzo(a)pyrene (BP) mediated a similar progenitor suppression up to 6 h, but reversal rapidly ensued. This recovery was absent in mice with a polycyclic aromatic hydrocarbon (PAH)‐resistant, AhRd genotype. This AhR‐dependent progenitor recovery with BP induction accounts for the absence of suppression of B220+ BM and spleen populations at 48–168 h. However, DMBA and BP produced similar profiles for thymus cell suppression, independent of AhR genotype. Thus, lymphoid progenitors may exit the BM to the thymus prior to the BP reversal. This progenitor recovery is associated with elevated chemokines and cytokines that depend on AhR‐mediated induction of CYP1A1. This response increased constitutively in Cyp1b1‐ko BM, demonstrating that CYP1B1 metabolizes local stimulants that impact a basal progenitor protection process.
