Differential Regulation of Lympho-Myelopoiesis by Stromal Cells in the Early and Late Phases in BALB/c Mice Repeatedly Exposed to Lipopolysaccharide.
Differential Regulation of Lympho-Myelopoiesis by Stromal Cells in the Early and Late Phases in BALB/c Mice Repeatedly Exposed to Lipopolysaccharide.
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DOI：
10.1248/bpb.b16-00375
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发表时间：
2016-12
影响因子：
2
通讯作者：
I. Tsuboi;Tomonori Harada;Y. Hirabayashi;J. Kanno;S. Aizawa
中科院分区：
文献类型：
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作者：
I. Tsuboi;Tomonori Harada;Y. Hirabayashi;J. Kanno;S. Aizawa
慢性脂多糖（LPS）暴露于小鼠，使淋巴细胞室减少，使造血细胞室向髓细胞倾斜，这被认为是LPS对造血干细胞的直接影响。然而，慢性LPS暴露对构成造血微环境的基质细胞的影响尚未阐明。在这里，我们研究了重复LPS暴露对基质细胞的早期和晚期影响。在早期，每周给小鼠注射5或25µg LPS 3次，每次治疗后骨髓（BM）中的骨髓祖细胞（集落形成单位-粒细胞巨噬细胞（CFU-GM））和B淋巴祖细胞（CFU-preB）的数量迅速减少。CFU-GM细胞的数量从最初的减少中恢复，然后增加到高于预处理水平，而CFU-preB细胞的数量仍然低于预处理水平。在骨髓中，粒细胞集落刺激因子（G-CSF）、粒细胞巨噬细胞集落刺激因子（GM-CSF）和白细胞介素(IL)-6等骨髓生成阳性调节基因和B淋巴生成负调节基因（肿瘤坏死因子(TNF)-α）的表达上调，而B淋巴生成阳性调节基因(基质细胞衍生因子(SDF)-1、IL-7和干细胞因子（SCF）的表达下调。在第一次用5µg和25µg LPS处理后70 d， CFU-preB细胞的数量仍低于预处理水平，而CFU-GM细胞的数量恢复到预处理水平。骨髓中IL-7基因表达继续下调，而SDF-1和SCF基因表达水平恢复。因此，慢性LPS暴露可能损害基质细胞功能，导致B淋巴生成的长期抑制，这可能表现为与血液学表型相似的衰老。
Chronic lipopolysaccharide (LPS) exposure to mice reduces the lymphoid compartment and skews the hematopoietic cell compartment toward myeloid-cells, which is considered to be a direct effect of LPS on hematopoietic stem cells. However, the effect of chronic LPS exposure on stromal-cells, which compose the hematopoietic microenvironment, has not been elucidated. Here, we investigated early- and late-phase effects of repeated LPS exposure on stromal-cells. During the early phase, when mice were treated with 5 or 25 µg LPS three times at weekly intervals, the numbers of myeloid-progenitor (colony forming unit-granulocyte macrophage (CFU-GM)) cells and B lymphoid-progenitor (CFU-preB) cells in the bone-marrow (BM) rapidly decreased after each treatment. The number of CFU-GM cells recovered from the initial decrease and then increased to levels higher than pretreatment levels, whereas the number of CFU-preB cells remained lower than pretreatment levels. In the BM, expression of genes for positive-regulators of myelopoiesis including granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), and interleukin (IL)-6 and negative-regulators of B lymphopoiesis including tumor necrosis factor (TNF)-α was up-regulated, whereas expression of positive-regulators of B lymphopoiesis including stromal cell-derived factor (SDF)-1, IL-7, and stem cell factor (SCF) was down-regulated. During the late phase, the number of CFU-preB cells remained lower than pretreatment levels 70 d after the first treatments with 5 and 25 µg LPS, whereas the number of CFU-GM cells returned to pretreatment levels. IL-7 gene expression in the BM remained down-regulated, whereas gene-expression levels of SDF-1 and SCF were restored. Thus, chronic LPS exposure may impair stromal-cell function, resulting in prolonged suppression of B lymphopoiesis, which may appear to be senescence similar to the hematological phenotype.