Lipopolysaccharide Reciprocally Alters the Stromal Cell-Regulated Positive and Negative Balance between Myelopoiesis and B Lymphopoiesis in C57BL/6 Mice
Lipopolysaccharide Reciprocally Alters the Stromal Cell-Regulated Positive and Negative Balance between Myelopoiesis and B Lymphopoiesis in C57BL/6 Mice
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DOI：
10.1248/bpb.b14-00279
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发表时间：
2014-12-01
影响因子：
2
通讯作者：
Aizawa, Shin
中科院分区：
文献类型：
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作者：
Taki, Masafumi;Tsuboi, Isao;Aizawa, Shin
骨髓(BM)和脾中的造血由基质细胞控制。炎症促进骨髓生成，同时抑制B淋巴细胞生成。然而，基质细胞对骨髓生成和B淋巴细胞生成的相互调节在炎症过程中的作用尚不完全清楚。我们研究了炎症诱导的内毒素(LPS)处理的小鼠造血调节的改变。C57BL/6雌性小鼠静脉注射5mU剂量的内毒素后，骨髓中粒细胞-巨噬细胞祖细胞(CFU-GM)和B细胞祖细胞(CFU-Preb)数量迅速减少。CFU-GM迅速恢复，而CFU-Preb恢复较慢。脂多糖诱导小鼠脾CFU-GM数明显增加，但CFU-Preb数无明显变化。经脂多糖治疗后，骨髓和脾中粒细胞集落刺激因子(G-CSF)、白细胞介素6(IL-6)、粒细胞巨噬细胞集落刺激因子(GM-CSF)基因表达水平明显上调，而基质细胞衍生因子(SDF)-1、干细胞因子(SCF)、IL-7等B淋巴细胞基因表达水平无明显变化。同时，B淋巴细胞生成的负性调节因子肿瘤坏死因子-α显著上调。经内毒素处理后，骨髓中S期CFU-GM数量增加，而S期CFU-Preb数量减少。这些结果提示，内毒素激活的基质细胞诱导正显性的骨髓生成和负显性的B淋巴细胞生成，通过抑制B淋巴细胞的生成，促进炎症过程中的紧急骨髓生成，从而有助于宿主抵抗感染。
Hematopoiesis in the bone marrow (BM) and spleen is controlled by stromal cells. Inflammation promotes myelopoiesis and simultaneously suppresses B lymphopoiesis. However, the role of the reciprocal regulation of myelopoiesis and B lymphopoiesis by stromal cells during inflammation is not fully understood. We investigated inflammation-induced alteration of hematopoietic regulation in lipopolysaccharide (LPS)-treated mice. C57BL/6 female mice were intravenously injected with a single, 5-mu g dose of LPS, which induced a rapid decrease in the number of granulocyte-macrophage progenitors (colony-forming unit granulocyte-macrophage; CFU-GM) and B cell progenitors (CFU-preB) in BM. The CFU-GM count rapidly recovered, whereas the recovery of CFU-preB was delayed. LPS induced a marked increase in the number of CFU-GM but not in the number of CFU-preB in spleen. After LPS treatment, gene expression levels of positive regulators of myelopoiesis such as granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in BM and spleen were markedly upregulated whereas levels of positive regulators for B lymphopoiesis such as stromal cell-derived factor (SDF)-1, stem cell factor (SCF), and IL-7 remained unchanged. Meanwhile, the negative regulator of B lymphopoiesis tumor necrosis factor (TNF)-alpha was markedly up-regulated. The number of CFU-GM in S-phase in BM increased after LPS treatment, whereas the number of CFU-preB in S-phase decreased. These results suggest that LPS-activated stromal cells induce positive-dominant regulation of myelopoiesis and negative-dominant regulation of B lymphopoiesis, which facilitates emergency myelopoiesis during inflammation by suppressing B lymphopoiesis, thereby contributing to the host defense against infection.