Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.
J Histochem Cytochem. 2019 Jan;67(1):9-27. doi: 10.1369/0022155418798770. Epub 2018 Sep 11.
Heparan sulfate (HS) proteoglycans on immune cells have the ability to bind to and regulate the bioactivity more than 400 bioactive protein ligands, including many chemokines, cytokines, and growth factors. This makes them important regulators of the phenotype and behavior of immune cells. Here we review how HS biosynthesis in macrophages is regulated during polarization and in chronic inflammatory diseases such as rheumatoid arthritis, atherosclerosis, asthma, chronic obstructive pulmonary disease and obesity, by analyzing published micro-array data and mechanistic studies in this area. We describe that macrophage expression of many HS biosynthesis and core proteins is strongly regulated by macrophage polarization, and that these expression patterns are recapitulated in chronic inflammation. Such changes in HS biosynthetic enzyme expression are likely to have a significant impact on the phenotype of macrophages in chronic inflammatory diseases by altering their interactions with chemokines, cytokines, and growth factors.
肝素硫酸(HS)蛋白聚糖在免疫细胞上具有结合和调节超过 400 种生物活性蛋白配体的能力,包括许多趋化因子、细胞因子和生长因子。这使它们成为免疫细胞表型和行为的重要调节剂。在这里,我们通过分析该领域发表的微阵列数据和机制研究,回顾了巨噬细胞极化过程中和类风湿关节炎、动脉粥样硬化、哮喘、慢性阻塞性肺疾病和肥胖等慢性炎症性疾病中 HS 生物合成如何受到调节。我们描述了许多 HS 生物合成和核心蛋白在巨噬细胞极化过程中的表达受到强烈调控,并且这些表达模式在慢性炎症中得到再现。HS 生物合成酶表达的这种变化很可能通过改变它们与趋化因子、细胞因子和生长因子的相互作用,对慢性炎症性疾病中巨噬细胞的表型产生重大影响。