Department of Veterinary Medicine, Universita degli Studi di Milano, Milano, Italy.
Curr Protein Pept Sci. 2019;20(6):505-524. doi: 10.2174/1389203720666190405101138.
α1-acid glycoprotein (orosomucoid, AGP) is an Acute Phase Protein produced by liver and peripheral tissues in response to systemic reaction to inflammation. AGP functions have been studied mostly in human, cattle and fish, although the protein has been also found in many mammalian species and birds. AGP fulfils at least two set of functions, which are apparently different from each other but in fact intimately linked. On one hand, AGP is an immunomodulatory protein. On the other hand, AGP is one of the most important binding proteins in plasma and, beside modulating pharmacokinetics and pharmacodynamics of many drugs, it is also able to bind and transport several endogen ligands related to inflammation. The focus of this review is the immunomodulatory activity of AGP. This protein regulates every single event related to inflammation, including binding of pathogens and modulating white blood cells activity throughout the entire leukocyte attacking sequence. The regulation of AGP activity is complex: the inflammation induces not only an increase in AGP serum concentration, but also a qualitative change in its carbohydrate moiety, generating a multitude of glycoforms, each of them with different, and sometimes opposite and contradictory, activities. We also present the most recent findings about the relationship between AGP and adipose tissue: AGP interacts with leptin receptor and, given its immunomodulatory function, it may be included among the potential players in the field of immunometabolism.
α1-酸性糖蛋白(orosomucoid,AGP)是一种急性相蛋白,由肝脏和外周组织产生,以响应全身对炎症的反应。AGP 的功能已在人类、牛和鱼类中进行了大量研究,尽管该蛋白也在许多哺乳动物和鸟类中被发现。AGP 至少履行了两套功能,这些功能显然彼此不同,但实际上却紧密相连。一方面,AGP 是一种免疫调节蛋白。另一方面,AGP 是血浆中最重要的结合蛋白之一,除了调节许多药物的药代动力学和药效学外,它还能够结合和转运与炎症相关的几种内源性配体。本文综述的重点是 AGP 的免疫调节活性。该蛋白调节与炎症相关的每一个单一事件,包括病原体的结合以及通过整个白细胞攻击序列调节白细胞的活性。AGP 活性的调节非常复杂:炎症不仅会增加血清 AGP 浓度,还会导致其碳水化合物部分发生质量变化,从而产生多种糖型,每种糖型都具有不同的、有时甚至相反和矛盾的活性。我们还介绍了最近关于 AGP 与脂肪组织之间关系的发现:AGP 与瘦素受体相互作用,并且鉴于其免疫调节功能,它可能被纳入免疫代谢领域的潜在参与者之列。