Miller John D, Stevens Elliott T, Smith Deandra R, Wight Thomas N, Wrenshall Lucile E
Division of Transplantation, University of Nebraska Medical Center, Omaha, NE 68198-7690, USA.
Immunol Cell Biol. 2008 Feb;86(2):192-9. doi: 10.1038/sj.icb.7100128. Epub 2007 Nov 27.
Although interleukin-2 (IL-2) is typically considered a soluble cytokine, our laboratory has shown that the availability of IL-2 in lymphoid tissues is regulated, in part, by an association with heparan sulfate glycosaminoglycan. Heparan sulfate is usually found in proteoglycan form, in which the heparan sulfate chains are covalently linked to a specific core protein. We now show that perlecan is one of the major IL-2-binding heparan sulfate proteoglycans in murine spleen. IL-2 binds perlecan via heparan sulfate chains, as enzymatic removal of heparan sulfate from splenic perlecan abolishes its ability to bind IL-2. Furthermore, we demonstrate that perlecan-bound IL-2 supports the proliferation of an IL-2-dependent cell line. Identification of perlecan as a major heparan sulfate proteoglycan that binds IL-2 has implications for both the localization and regulation of IL-2 in vivo.
尽管白细胞介素-2(IL-2)通常被认为是一种可溶性细胞因子,但我们实验室已表明,淋巴组织中IL-2的可用性部分是通过与硫酸乙酰肝素糖胺聚糖的结合来调节的。硫酸乙酰肝素通常以蛋白聚糖的形式存在,其中硫酸乙酰肝素链与特定的核心蛋白共价连接。我们现在表明,基底膜聚糖是小鼠脾脏中主要的IL-2结合硫酸乙酰肝素蛋白聚糖之一。IL-2通过硫酸乙酰肝素链与基底膜聚糖结合,因为从脾脏基底膜聚糖上酶促去除硫酸乙酰肝素会消除其结合IL-2的能力。此外,我们证明与基底膜聚糖结合的IL-2支持IL-2依赖性细胞系的增殖。将基底膜聚糖鉴定为结合IL-2的主要硫酸乙酰肝素蛋白聚糖对体内IL-2的定位和调节都有影响。