Fernandez-Botran R, Yan J, Justus D E
Division of Experimental Immunology and Immunopathology, Department of Pathology and Laboratory Medicine, University of Louisville, KY 40292, USA.
Cytokine. 1999 May;11(5):313-25. doi: 10.1006/cyto.1998.0438.
Glycosaminoglycans (GAGs) are a group of negatively charged molecules present in many tissues as components of the extracellular matrix, basement and cellular membranes. This work analysed the ability of this group of substances to interact with human interferon gamma and the effect of those interactions on its biologic activity. A variety of GAGs (heparin, heparan sulfate, chondroitin sulfate and hyaluronic acid), and a related sulfated polysaccharide (dextran sulfate), were found to interact with IFN-gamma as determined by inhibition of the binding of [125I]IFN-gamma to COLO-205 cells and binding to wells coated with GAGs. These interactions were inhibited by synthetic peptides mimicking the sequences of the basic amino acid cluster located at the C-terminal end of mouse and human IFN-gamma, or by poly-L-lysine, suggesting that ionic interactions between the positively-charged C-terminus and negatively charged groups in GAGs were involved. IFN-gamma molecules bound to plate-immobilized or endothelial cell surface GAGs retained biological activity, since they could induce major histocompatibility complex (MHC) class II expression on COLO-205 cells, suggesting that cell surface GAGs might be able to present IFN-gamma to its receptors. These results suggest important regulatory roles for GAGs on the activity of IFN-gamma in vivo.
糖胺聚糖（GAGs）是一组带负电荷的分子，作为细胞外基质、基底膜和细胞膜的组成成分存在于许多组织中。本研究分析了这类物质与人类干扰素γ相互作用的能力，以及这些相互作用对其生物学活性的影响。通过抑制[125I]干扰素γ与COLO-205细胞的结合以及与包被有GAGs的孔的结合，发现多种GAGs（肝素、硫酸乙酰肝素、硫酸软骨素和透明质酸）以及一种相关的硫酸化多糖（硫酸葡聚糖）能与干扰素γ相互作用。模拟小鼠和人类干扰素γ C末端碱性氨基酸簇序列的合成肽或聚-L-赖氨酸可抑制这些相互作用，这表明带正电荷的C末端与GAGs中带负电荷基团之间的离子相互作用参与其中。结合在平板固定化或内皮细胞表面GAGs上的干扰素γ分子保留了生物学活性，因为它们能诱导COLO-205细胞上主要组织相容性复合体（MHC）II类分子的表达，这表明细胞表面GAGs可能能够将干扰素γ呈递给其受体。这些结果提示GAGs在体内对干扰素γ的活性具有重要的调节作用。
