Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T
Department of Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Japan.
Nature. 1996 Aug 15;382(6592):635-8. doi: 10.1038/382635a0.
The chemokines are a large family of small, structurally related cytokines. The physiological importance of most members of this family has yet to be elucidated, although some are inducible inflammatory mediators that determine leukocyte chemotaxis. Pre-B-cell growth-stimulating factor/stromal cell-derived factor-1 (PBSF/SDF-1) is a member of the CXC group of chemokines PBSF/SDF-1 stimulates proliferation of B-cell progenitors in vitro and is constitutively expressed in bone-marrow-derived stromal cells. 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 mice 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 bone 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.
趋化因子是一大类结构相关的小细胞因子。尽管该家族的一些成员是可诱导的炎症介质，可决定白细胞趋化性，但这个家族大多数成员的生理重要性尚未阐明。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。PBSF/SDF-1在体外刺激B细胞祖细胞的增殖，并在骨髓来源的基质细胞中组成性表达。在此，我们通过生成编码PBSF/SDF-1的基因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的小鼠在围产期死亡，并且尽管突变胚胎中B细胞祖细胞的数量在胎儿肝脏和骨髓中严重减少，但髓系祖细胞仅在骨髓中减少，而在胎儿肝脏中未减少，这表明PBSF/SDF-1负责B细胞淋巴细胞生成和骨髓髓细胞生成。此外，突变体有室间隔缺损。因此，我们已表明趋化因子PBSF/SDF-1在发育中有几种重要功能。
