McCarthy Cormac, Saldova Radka, Wormald Mark R, Rudd Pauline M, McElvaney Noel G, Reeves Emer P
Respiratory Research Division, Royal College of Surgeons in Ireland , Beaumont Hospital, Dublin 9, Ireland.
J Proteome Res. 2014 Jul 3;13(7):3131-43. doi: 10.1021/pr500146y. Epub 2014 Jun 12.
Acute phase proteins (APPs) are a group of circulating plasma proteins which undergo changes quantitatively or qualitatively at the time of inflammation. Many of these APPs are glycosylated, and it has been shown that alterations in glycosylation may occur in inflammatory and malignant conditions. Changes in glycosylation have been studied as potential biomarkers in cancer and also in chronic inflammatory conditions and have been shown to correlate with disease severity in certain conditions. Serine protease inhibitors (serpins), many of which are also APPs, are proteins involved in the control of proteases in numerous pathways. Alpha-1 Antitrypsin (AAT) is the most abundant serpin within the circulation and is an APP which has been shown to increase in response to inflammation. The primary role of AAT is maintaining the protease/antiprotease balance in the lung, but it also possesses important anti-inflammatory and immune-modulating properties. Several glycoforms of AAT exist, and they possess differing properties in regard to plasma half-life and stability. Glycosylation may also be important in determining the immune modulatory properties of AAT. The review will focus on the role and importance of glycosylation in acute phase proteins with particular attention to AAT and its use as a biomarker of disease. The review describes the processes involved in glycosylation, how glycosylation changes in differing disease states, and the alterations that occur to glycans of APPs with disease and inflammation. Finally, the review explores the importance of changes in glycosylation of AAT at times of inflammation and in malignant conditions and how this may impact upon the functions of AAT.
急性期蛋白（APPs）是一组循环血浆蛋白，在炎症发生时其数量或质量会发生变化。这些APPs中的许多都是糖基化的，并且已经表明糖基化改变可能发生在炎症和恶性疾病状态中。糖基化变化已作为癌症以及慢性炎症性疾病的潜在生物标志物进行研究，并已表明在某些情况下与疾病严重程度相关。丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制因子），其中许多也是APPs，是参与众多途径中蛋白酶控制的蛋白质。α-1抗胰蛋白酶（AAT）是循环中最丰富的丝氨酸蛋白酶抑制因子，是一种已被证明会随着炎症反应而增加的APP。AAT的主要作用是维持肺内蛋白酶/抗蛋白酶平衡，但它也具有重要的抗炎和免疫调节特性。AAT存在几种糖型，它们在血浆半衰期和稳定性方面具有不同的特性。糖基化在确定AAT的免疫调节特性方面也可能很重要。本综述将重点关注糖基化在急性期蛋白中的作用和重要性，特别关注AAT及其作为疾病生物标志物的用途。该综述描述了糖基化所涉及的过程、糖基化在不同疾病状态下如何变化以及APPs的聚糖在疾病和炎症时发生的改变。最后，该综述探讨了炎症和恶性疾病状态下AAT糖基化变化的重要性以及这可能如何影响AAT的功能。
