Klein G, Conzelmann S, Beck S, Timpl R, Müller C A
University Medical Clinic, Department of Internal Medicine II, Tübingen.
Matrix Biol. 1995 Feb;14(6):457-65. doi: 10.1016/0945-053x(95)90003-9.
Human perlecan is a heparan sulfate proteoglycan with a large core protein of 467 kDa to which three glycosaminoglycan side chains are attached. It belongs to the heparan sulfate proteoglycan family which has been implicated in strong interactions between developing hematopoietic cells and their microenvironment in the bone marrow. Here we report that perlecan is highly expressed in the human bone marrow, as well as in long-term bone marrow cultures which are thought to mimic hematopoiesis in vitro. Expression of perlecan in this tissue was shown by Northern blotting of the 14-kb mRNA of the core protein and by immunofluorescence stainings. Functionally, perlecan shows a strong anti-adhesive effect on unfractionated bone marrow cells and on various hematopoietic cell lines, repelling the cells from the perlecan-coated area. In contrast, perlecan is adhesive for fibroblasts and endothelial cells. It is suggested that the anti-adhesive site is located within the core protein of perlecan since heparitinase-treated perlecan still shows the repellent effect. Although anti-adhesive for hematopoietic cells, perlecan is able to bind growth factors like granulocyte/macrophage-colony stimulating factor and present them to hematopoietic progenitor cells in a semi-solid colony assay. The functional role of a growth-factor-binding extracellular matrix component in the bone marrow microenvironment with anti-adhesive properties is uncertain but may be related to compartmentalization.
人核心蛋白聚糖是一种硫酸乙酰肝素蛋白聚糖，其核心蛋白很大，为467 kDa，连接有三条糖胺聚糖侧链。它属于硫酸乙酰肝素蛋白聚糖家族，该家族与发育中的造血细胞及其骨髓微环境之间的强烈相互作用有关。在此我们报告，核心蛋白聚糖在人骨髓以及被认为可在体外模拟造血作用的长期骨髓培养物中高度表达。通过对核心蛋白1 . 4 kb mRNA进行Northern印迹分析以及免疫荧光染色，证实了核心蛋白聚糖在该组织中的表达。在功能上，核心蛋白聚糖对未分离的骨髓细胞和各种造血细胞系显示出强烈的抗黏附作用，使细胞从包被有核心蛋白聚糖的区域排斥开。相反，核心蛋白聚糖对成纤维细胞和内皮细胞具有黏附性。由于经肝素酶处理的核心蛋白聚糖仍显示出排斥作用，提示抗黏附位点位于核心蛋白聚糖的核心蛋白内。虽然核心蛋白聚糖对造血细胞具有抗黏附性，但在半固体集落试验中，它能够结合粒细胞/巨噬细胞集落刺激因子等生长因子并将其呈递给造血祖细胞。具有抗黏附特性的生长因子结合细胞外基质成分在骨髓微环境中的功能作用尚不确定，但可能与分隔作用有关。
