COMPARTMENTALIZATION OF A HEMATOPOIETIC GROWTH-FACTOR (GM-CSF) BY GLYCOSAMINOGLYCANS IN THE BONE-MARROW MICROENVIRONMENT
COMPARTMENTALIZATION OF A HEMATOPOIETIC GROWTH-FACTOR (GM-CSF) BY GLYCOSAMINOGLYCANS IN THE BONE-MARROW MICROENVIRONMENT
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DOI：
10.1038/326403a0
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发表时间：
1987-03-26
期刊：
影响因子：
64.8
通讯作者：
GREAVES, MF
中科院分区：
文献类型：
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作者：
GORDON, MY;RILEY, GP;GREAVES, MF
当受到外源造血细胞生长因子 (HCGF)（例如粒细胞巨噬细胞集落刺激因子 (GM-CSF)1,2）刺激时，造血祖细胞在半固体培养基中增殖并成熟。它们还与骨髓基质细胞一起增殖3,4，尽管在基质培养上清液中无法检测到具有生物活性的 HCGF 量 5。 HCGF 可能由基质细胞少量合成，但仍与基质细胞和/或其细胞外基质 (ECM) 结合。这种解释符合长期培养中与基质层密切相关的造血祖细胞增殖6。糖胺聚糖 (GAG) 存在于基质细胞产生的 ECM 中27,8。它们是选择性地将 HCGF 保留在基质层中的主要候选者 9；它们影响胚胎形态发生和细胞分化10，并且可能调节造血作用11-13。我们现在报道，粒细胞-巨噬细胞集落刺激活性可以从培养的基质层中洗脱，并且外源性 GM-CSF 与来自骨髓基质 ECM 的 GAG 结合。 HCGF 以这种方式的选择性区室化可能是骨髓微环境的重要功能，并且可能参与造血细胞调节。
Haematopoietic progenitor cells proliferate and mature in semi-solid media when stimulated by exogenous haematopoietic cell growth factors (HCGFs) such as granulocyte-macrophage colony-stimulating factor (GM-CSF)1,2. They also proliferate in association with marrow-derived stromal cells3,4although biologically active amounts of HCGFs cannot be detected in stromal culture supernatants5. It is possible that HCGFs are synthesized in small amounts by stromal cells but remain bound to the stromal cells and/or their extracellular matrix (ECM). This interpretation accords with haematopoietic progenitor cell proliferation in close association with stromal layers in long-term cultures6. Glycosaminoglycans (GAGs) are found in the ECM produced by stromal cells27,8. They are prime candidates for selectively retaining HCGFs in the stromal layer9; they influence embryonic morphogenesis and cyto-differentiation10and they may regulate haematopoiesis11–13. We now report that granulocyte-macrophage colony-stimulating activity can be eluted from cultured stromal layers and that exogenous GM-CSF binds to GAGs from bone marrow stromal ECM. Selective Compartmentalization of HCGFs in this manner may be an important function of the marrow microenvironment and may be involved in haematopoietic cell regulation.