Gordon M Y, Riley G P, Clarke D
Leukaemia Research Fund Centre, Institute of Cancer Research, London, U.K.
Leukemia. 1988 Dec;2(12):804-9.
Human hemopoietic blast colony-forming cells (BI-CFCs) recognize and adhere to the extracellular matrix (ECM) produced by marrow-derived stromal cells in vitro. We have investigated the requirements for this interaction by testing the capacity of BI-CFCs to adhere to ECM components under a variety of conditions. Binding was prevented completely by prior treatment of stromal ECM with nitrous acid, in large part by treatment with heparitinase or hyaluronidase, and slightly by treatment with chondroitinases. Whereas heparan sulfate isolated from marrow stromal cultures effectively blocked binding, heparan sulfate from bovine kidney did not. Chondroitin sulfate and hyaluronic acid did not have any effect in this test. In contrast, collagen was not sufficient for the interaction because dishes coated with collagen type I or IV did not act as adhesive surfaces for BI-CFCs. Ligands for integrin receptors (e.g., fibronectin) did not participate in BI-CFC binding because the synthetic pentapeptide glycine-arginine-glycine-asparagine-serine did not compete with stroma in binding BI-CFCs. These findings indicate that heparan sulfate in the bone marrow microenvironment is necessary for BI-CFC binding to ECM and may contribute to localizing hemopoietic stem cells in hemopoietic tissue.
人造血母细胞集落形成细胞(BI-CFCs)在体外能够识别并黏附于骨髓来源的基质细胞产生的细胞外基质(ECM)。我们通过检测BI-CFCs在多种条件下黏附于ECM成分的能力,研究了这种相互作用的必要条件。用亚硝酸预先处理基质ECM可完全阻止结合,用肝素酶或透明质酸酶处理可在很大程度上阻止结合,用软骨素酶处理则有轻微阻止作用。从骨髓基质培养物中分离的硫酸乙酰肝素可有效阻断结合,而从牛肾中提取的硫酸乙酰肝素则不能。硫酸软骨素和透明质酸在此试验中没有任何作用。相反,胶原蛋白不足以介导这种相互作用,因为用I型或IV型胶原蛋白包被的培养皿不能作为BI-CFCs的黏附表面。整合素受体的配体(如纤连蛋白)不参与BI-CFC的结合,因为合成的五肽甘氨酸-精氨酸-甘氨酸-天冬酰胺-丝氨酸在结合BI-CFCs时不能与基质竞争。这些发现表明,骨髓微环境中的硫酸乙酰肝素是BI-CFCs黏附于ECM所必需的,可能有助于造血干细胞在造血组织中的定位。