人胎肝中一种35kD成分的造血调控研究

STUDIES OF A 35 KDa SUBSTANCE FROM HUMAN FETAL LIVER ON THE REGULATION OF HEMATOPOIESIS

３－５月胎龄人肝脏造血异常活跃。其中造血干细胞约有３０－４０％处于细胞周期Ｓ期，远高于成年骨髓中约１０％的比例。胎肝中存在活性很高血的造血干细胞增殖刺激因子可能是这一活跃功能的分子基础。基于这种事实，本文用小鼠ＣＦＵ－Ｓ“自杀”率对这种活性进行了检测。经过多步分离纯化，获得一分子量约３５ｋＤ的单一活性组分，定名为ＦＬＳ－４。ＦＬＳ－４作用于脐带血ＣＤ３４细胞，使其＾３Ｈ－ＴｄＲ掺入率提高近１倍。

About 30%-40% of hematopoietic stem cells in human fetal liver of 3-5 months are in S phase of cell cycle, much higer than the ratio of 10% of that in adult bone marrow. The existance of highly active hematopoietic stem cell proliferation stimulators is probably its molecular basis. CFU-S 'suicide rate' in rats was adopted to detect the effective substance. Through several steps of separation, we obtained a relatively purified substance of 35kDa, termed it as FLS-4. CD 34 positive cord blood cells were sorted and assayed for their response to FLS-4 in 3H-TdR incorporation assay. The response to FLS-4 alone was approximately 1 times the background response seen with no factor added. In combination with IL-6 and IL-3 produced response that was 2.9 and 6.5 fold respectively greater than that observed with no factor added, but was weakly in comparison with the effects of SCF. In combination with GM-CSF or IL-3, FLS-4 can stimulate the formation of blast-colonies. The results indicate that the FLS-4 is very likely to be a novel hematopoietic stem cell proliferation stimulator. In physical or biological characteristics, it exhibited a Unique character different from IL-3, IL-6, GM-CSF,SCF or FLT3 ligand those are known to have hematopoietic stem cell prolifcration stimulating activity. During the period of active he-matopoiesis in fetal liver, FLS-4 might be the candidate in triggering hematopoietic stem cells from resting G0 to S phase.