Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1
Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1
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DOI：
10.1038/382635a0
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发表时间：
1996-08-15
期刊：
影响因子：
64.8
通讯作者：
Kishimoto, T
中科院分区：
文献类型：
--
作者：
Nagasawa, T;Hirota, S;Kishimoto, T
趋化因子是一个大家族的小，结构相关的细胞因子（1，2）。该家族大多数成员的生理重要性尚未阐明，尽管有些是决定白细胞趋化性的诱导性炎症介质（1-5）。前B细胞生长刺激因子/基质细胞衍生因子-1（PBSF/SDF-1）是趋化因子CXC组的成员（6，7）。PBSF/SDF-1在体外刺激B细胞祖细胞增殖（6），并在骨髓源性基质细胞中组成型表达（6，7）。在这里，我们通过产生具有编码PBSF/SDF-1的基因的靶向破坏的突变小鼠来研究PBSF/SDF-1的生理作用。我们发现缺乏PBSF/SDF-1的螨在围产期死亡，并且尽管突变胚胎中的B细胞祖细胞的数量在胎肝和骨髓中严重减少，但髓样祖细胞仅在骨髓中减少，而在胎肝中不减少，表明PBSF/SDF-1负责B细胞淋巴细胞生成和骨髓骨髓生成。此外，突变体具有心脏室间隔缺损，因此，我们已经表明趋化因子PBSF/SDF-1在发育中具有几种基本功能。
THE chemokines are a large family of small, structurally related cytokines(1,2). The physiological importance of most members of this family has yet to be elucidated, although some are inducible inflammatory mediators that determine leukocyte chemotaxis(1-5). Pre-B-cell growth-stimulating factor/stromal cell-derived factor-1 (PBSF/SDF-1) is a member of the CXC group of chemokines(6,7). PBSF/SDF-1 stimulates proliferation of B-cell progenitors in vitro(6) and is constitutively expressed in bone-marrow-derived stromal cells(6,7). Here we investigate the physiological roles of PBSF/SDF-1 by generating mutant mice with a targeted disruption of the gene encoding PBSF/SDF-1, We found that mite lacking PBSF/SDF-1 died perinatally and that although the numbers of B-cell progenitors in mutant embryos were severely reduced in fetal liver and bone marrow, myeloid progenitors were reduced only in the hone marrow but not in the fetal liver, indicating that PBSF/SDF-1 is responsible for B-cell lymphopoiesis and bone-marrow myelopoiesis. In addition, the mutants had a cardiac ventricular septal defect, Hence, we have shown that the chemokine PBSF/SDF-1 has several essential functions in development.