标题：The role of heparin/heparan sulphate in the IFN-gamma-led Arena
作者：Xu, Kening; Jin, Lan
作者机构：[Xu, Kening; Jin, Lan] Shandong Univ, Natl Glycoengn Res Ctr, Shandong Key Lab Carbohydrate Chem & Glycobiol, Qingdao 266000, Shandong, Peoples R Chin 更多 通讯作者地址：Jin, L (corresponding author), Shandong Univ, Natl Glycoengn Res Ctr, Shandong Key Lab Carbohydrate Chem & Glycobiol, Qingdao 266000, Shandong, People 更多
关键词：IFN-gamma; Heparin; Heparan sulphate; Structure-activity relationship
摘要：IFN-gamma (Interferon-gamma) is a pleiotropic cytokine. It is often involved in a variety of physiological processes by binding to the cell surface transmembrane receptor (IFN-gamma R) to initiate a series of signalling pathways that transmit external signals from cell surface receptors to the cell nucleus. Heparan sulphate (HS), a highly sulphated linear polysaccharide, is ubiquitous on the mammalian cell surface and extracellular matrix. Electrostatic interactions can be generated between the highly sulphated HS region and specific basic amino acid residues in the IFN-gamma structure, thereby detaining IFN-gamma on the cell surface, and the concentration of IFN-gamma on the cell surface is thus, changed. IFN-gamma retained on the cell surface will optimize the binding of IFN-gamma to the transmembrane receptor resulting in high efficiency signalling. Heparin is a glycosaminoglycan with a structure similar to HS. The structural similarity provides a basis for modelling exogenous heparin dependence for interference with IFN-gamma function. This model can be summarized as follows: First, the competitive binding effect; heparin bound to cytokines by competing with membrane-associated HS, causes a decrease in cytokine concentration on the cell surface. Second, the principle of priority occupancy; heparin can occupy the receptor binding site on cytokines, partially preventing the IFN-gamma-IFN-gamma R interaction. These two models interfere with IFN-gamma signal transmission. To decipher the mechanism by which heparin influences IFN-gamma activity, studies of the structure-activity relationship are in progress. This paper summarizes research progress on the IFN-gamma signalling pathway, heparin interference with IFN-gamma activity and the structure-activity relationship between heparin and IFN-gamma. (C) 2019 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.