Milner C M, Higman V A, Day A J
MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, UK.
Biochem Soc Trans. 2006 Jun;34(Pt 3):446-50. doi: 10.1042/BST0340446.
TSG-6 is a multifunctional protein that is up-regulated in many pathological and physiological contexts, where it plays important roles in inflammation and tissue remodelling. For example, it is a potent inhibitor of neutrophil migration and can modulate the protease network through inhibition of plasmin. TSG-6 binds a wide range of GAGs (glycosaminoglycans) [i.e. HA (hyaluronan), chondroitin 4-sulphate, dermatan sulphate, heparin and heparan sulphate] as well as a variety of protein ligands, where these interactions can influence the activities of TSG-6. For example, through its association with HA, TSG-6 can mediate HA cross-linking via several different mechanisms, some of which promote leucocyte adhesion. Binding to heparin, however, enhances the ability of TSG-6 to potentiate the anti-plasmin activity of inter-alpha-inhibitor, which binds non-covalently to TSG-6 via its bikunin chain. Furthermore, although HA and heparin interact with distinct sites on the Link module, the binding of heparin can inhibit subsequent interaction with HA. In addition, the interactions of TSG-6 with HA, heparin and at least some of its protein ligands are sensitive to pH. Therefore it seems that in different tissue micro-environments (characterized, for example, by pH and GAG content), TSG-6 could be partitioned into functional pools with distinct activities.
TSG-6是一种多功能蛋白，在许多病理和生理环境中表达上调，在炎症和组织重塑中发挥重要作用。例如，它是中性粒细胞迁移的有效抑制剂，可通过抑制纤溶酶来调节蛋白酶网络。TSG-6能结合多种糖胺聚糖（即透明质酸、硫酸软骨素4、硫酸皮肤素、肝素和硫酸乙酰肝素）以及多种蛋白质配体，这些相互作用会影响TSG-6的活性。例如，通过与透明质酸结合，TSG-6可通过几种不同机制介导透明质酸交联，其中一些机制会促进白细胞黏附。然而，与肝素结合可增强TSG-6增强α-抑制剂间抗纤溶酶活性的能力，α-抑制剂间通过其比库宁链与TSG-6非共价结合。此外，尽管透明质酸和肝素与Link模块上的不同位点相互作用，但肝素的结合可抑制随后与透明质酸的相互作用。另外，TSG-6与透明质酸、肝素以及至少一些蛋白质配体的相互作用对pH敏感。因此，在不同的组织微环境（例如以pH和糖胺聚糖含量为特征）中，TSG-6似乎可被分配到具有不同活性的功能池中。
