Bruno E, Luikart S D, Long M W, Hoffman R
SyStemix, Palo Alto, CA, USA.
Exp Hematol. 1995 Oct;23(11):1212-7.
Heparan sulfate proteoglycan (HS-PG), an important component of the human bone marrow extracellular matrix (ECM), is believed to influence hematopoietic progenitor cell development by binding and localizing growth factors to specific niches within the hematopoietic microenvironment. We utilized a model ECM system, which uses immobilized ECM proteins and/or cytokines and bone marrow populations enriched for human hematopoietic stem cell (HSC), to assess the effects of HS-PG on the development of primitive hematopoietic progenitor cells. HS-PG alone failed to bind hematopoietic progenitor cells cloned from bone marrow CD34+CD15-HLA-DR- cells, which are enriched for HSC. HS-PG alone failed to function as a mitogen. In sharp contrast, the interaction of HS-PG with either growth factors (interleukin-3 [IL-3] or stem cell factor/Kit ligand [KL] or an ECM protein (thrombospondin [TSP]) markedly influenced progenitor cell adherence. The binding of either IL-3 or KL to HS-PG resulted in a two-fold increase in attachment of the colony-forming unit-granulocyte/macrophage (CFU-GM), a 1.5-fold increase in attachment of the burst-forming unit-erythroid (BFU-E) and the high-proliferative-potential colony-forming cell (HPP-CFC), and a two- to three-fold increase in attachment of the colony-forming unit-granulocyte/erythroid/macrophage/megakaryocyte (CFU-GEMM) compared to localized growth factor alone. Attachment of the BFU-megakaryocyte (BFU-MK), however, was slightly reduced by the interaction of either IL-3 or KL with HS-PG. The interaction of HS-PG with TSP resulted in a two-fold increase in CFU-GM and CFU-GEMM attachment, while the attachment of BFU-E, HPP-CFC, and BFU-MK was unaltered. We conclude that HS-PG cooperatively interacts with both growth factors and ECM proteins to augment progenitor cell localization within the hematopoietic microenvironment.
硫酸乙酰肝素蛋白聚糖（HS-PG）是人类骨髓细胞外基质（ECM）的重要组成部分，据信它通过将生长因子结合并定位到造血微环境内的特定生态位来影响造血祖细胞的发育。我们利用了一种模型ECM系统，该系统使用固定化的ECM蛋白和/或细胞因子以及富集人类造血干细胞（HSC）的骨髓群体，来评估HS-PG对原始造血祖细胞发育的影响。单独的HS-PG无法结合从富含HSC的骨髓CD34+CD15-HLA-DR-细胞克隆而来的造血祖细胞。单独的HS-PG不能作为有丝分裂原发挥作用。与之形成鲜明对比的是，HS-PG与生长因子（白细胞介素-3 [IL-3] 或干细胞因子/Kit配体 [KL]）或ECM蛋白（血小板反应蛋白 [TSP]）的相互作用显著影响祖细胞的黏附。IL-3或KL与HS-PG的结合导致集落形成单位 - 粒细胞/巨噬细胞（CFU-GM）的黏附增加两倍，爆式红系集落形成单位（BFU-E）和高增殖潜能集落形成细胞（HPP-CFC）的黏附增加1.5倍，以及集落形成单位 - 粒细胞/红系/巨噬细胞/巨核细胞（CFU-GEMM）的黏附相较于单独的局部生长因子增加两到三倍。然而，IL-3或KL与HS-PG的相互作用使巨核细胞爆式集落形成单位（BFU-MK）的黏附略有降低。HS-PG与TSP的相互作用导致CFU-GM和CFU-GEMM的黏附增加两倍，而BFU-E、HPP-CFC和BFU-MK的黏附未改变。我们得出结论，HS-PG与生长因子和ECM蛋白协同相互作用，以增强造血微环境内祖细胞的定位。
