Borghesi L A, Yamashita Y, Kincade P W
Oklahoma Medical Research Foundation, Immunobiology and Cancer Program, Oklahoma City 73104, USA.
Blood. 1999 Jan 1;93(1):140-8.
Heparin/heparan sulfate proteoglycans (HSPGs) have the potential to bind and directly regulate the bioactivity of hematopoietic growth factors including interleukin-7 (IL-7), a cytokine critical for murine B-cell development. We examined the consequence of manipulating soluble heparin and cell-surface heparan sulfate to IL-7-dependent responses of B-cell precursors. Soluble heparin was found to inhibit production of lymphoid, but not myeloid, cells in long-term bone marrow cultures. Analysis of pro-B cells lacking plasma membrane HS suggests that this glycosaminoglycan is required for efficient binding and responsiveness to IL-7. By contrast, responses of hematopoietic cells to other cytokines were not influenced by heparin addition or HS removal. Therefore, HSPGs on B-lineage precursors may function as IL-7 receptor components similar to HSPGs known to be important for the bFGF receptor. Other experiments suggest that HSPGs on the surface of stromal cells provide a weakly associating docking site for IL-7, possibly controlling availability of this cytokine to B-cell precursors. Together these data demonstrate a direct role for heparinlike molecules in regulating the IL-7-dependent stages of murine B lymphopoiesis.
肝素/硫酸乙酰肝素蛋白聚糖（HSPGs）有可能结合并直接调节造血生长因子的生物活性，这些因子包括白细胞介素-7（IL-7），它是对小鼠B细胞发育至关重要的一种细胞因子。我们研究了操控可溶性肝素和细胞表面硫酸乙酰肝素对B细胞前体IL-7依赖性反应的影响。在长期骨髓培养中发现可溶性肝素可抑制淋巴细胞而非髓细胞的生成。对缺乏质膜硫酸乙酰肝素的前B细胞的分析表明，这种糖胺聚糖对于有效结合IL-7并对其产生反应是必需的。相比之下，造血细胞对其他细胞因子的反应不受添加肝素或去除硫酸乙酰肝素的影响。因此，B系前体细胞上的HSPGs可能作为IL-7受体成分发挥作用，类似于已知对碱性成纤维细胞生长因子（bFGF）受体重要的HSPGs。其他实验表明，基质细胞表面的HSPGs为IL-7提供了一个弱结合的停靠位点，可能控制这种细胞因子对B细胞前体的可用性。这些数据共同证明了类肝素分子在调节小鼠B淋巴细胞生成的IL-7依赖性阶段中的直接作用。
