Mizon C, Mairie C, Balduyck M, Hachulla E, Mizon J
Laboratoire de Biochimie, Faculté de Pharmacie, Lille, France; Service de Médecine Interne, Hopital Cl. Huriez, Lille, France.
Eur J Biochem. 2001 May;268(9):2717-24. doi: 10.1046/j.1432-1327.2001.02168.x.
Inter-alpha-inhibitor (IalphaI) and pre-alpha-inhibitor (PalphaI) are the main members of a set of multichain serine proteinase inhibitors. Present in human plasma, they may be involved in control of the inflammatory process. They are composed of homologous heavy chains (H1 and H2 for IalphaI; H3 for PalphaI) covalently linked by a protein-glycosaminoglycan-protein cross-link to bikunin, which is a chondroitin 4-sulfate proteoglycan. During the acute-phase response, biosynthesis of IalphaI and PalphaI is downregulated and upregulated, respectively. In this work, we provide evidence that, in inflammatory diseases, the chondroitin sulfate chain of bikunin increases in size proportionally to the severity of the inflammatory response. As a consequence, all IalphaI-related components that contain bikunin are structurally modified. Therefore, the changes in glycosylation of the acute-phase proteins are not restricted to N-linked glycans but also affect glycosaminoglycans. The implications of these findings are discussed with regard to biosynthesis and biological role, especially the anti-inflammatory effects of IalphaI-related proteinase inhibitors.
α-间抑制因子（IαI）和前α-抑制因子（PαI）是一组多链丝氨酸蛋白酶抑制剂的主要成员。它们存在于人体血浆中，可能参与炎症过程的调控。它们由同源重链（IαI的H1和H2；PαI的H3）通过蛋白质-糖胺聚糖-蛋白质交联共价连接到比基尼，比基尼是一种硫酸软骨素4-硫酸蛋白聚糖。在急性期反应期间，IαI和PαI的生物合成分别下调和上调。在这项工作中，我们提供证据表明，在炎症性疾病中，比基尼的硫酸软骨素链大小与炎症反应的严重程度成比例增加。因此，所有含有比基尼的IαI相关成分在结构上都发生了改变。因此，急性期蛋白糖基化的变化不仅限于N-连接聚糖，还会影响糖胺聚糖。我们讨论了这些发现对于生物合成和生物学作用的意义，特别是IαI相关蛋白酶抑制剂的抗炎作用。
