The Acute Phase Protein α1-Acid Glycoprotein: A Model for Altered Glycosylation During Diseases

Abstract

Glycosylation is one of the most important post-translational modifications of proteins, and has been widely acknowledged as one of the most important ways to modulate both protein function and lifespan. The acute phase proteins are a major group of serum proteins whose concentration is altered during various pathophysiological conditions. The aim of this paper is to review the structure and functions of the alpha1-acid glycoprotein (AGP). AGP belongs to the subfamily of immunocalins, a group of binding proteins that also have immunomodulatory functions. One of the most interesting features of AGP is that its glycosylation microheterogeneity can be modified during diseases. This aspect is particularly remarkable, since both the immunomodulatory and the binding properties of AGP strongly depend on its carbohydrate composition. For these reasons, AGP can be considered an outstanding model for the study of glycan pattern modification during diseases. This review is focused on the most recent studies on the occurrence of different glycoforms in plasma and tissues and how the appearance of different oligosaccharide patterns during systemic inflammation or diseases can influence AGP's biological functions. The first part of the review will describe the structure of AGP and the several biological functions identified so far for this protein. The second part will be devoted to the post-translational modifications of the oligosaccharides micro-heterogeneity of AGP caused by pathological states. A critical evaluation of the impact of different AGP glycoforms on both its transport and anti-inflammatory features, and how the modifications of the glycan pattern can be utilized in clinical biochemistry, is also discussed.

Effects of intramammary infection on whey proteinograms of sheep during lactation

“…We believe that it is linked to the inflammatory process of the mammary gland because it has been identified only in infected glands. Its extra-hepatic productions has been reported previously in the epithelial cells of the mammary glands of humans and cattle (Ceciliani et al 2005, Rainard & Riollet 2006, Ceciliani & Pocacqua 2007.…”

“…Although the precise role of the α-1-acid glycoprotein remains elusive, studies suggest that it binds to a series of endogenous metabolites at the site of inflammation and acts on the innate immune response against infections thus modulating the immune reaction through the inhibition of phagocytosis, neutrophils activation, and platelet aggregation (Ceciliani & Pocacqua 2007, Eckersall 2008. Activated leukocytes may also act as a local source of α-1-acid glycoprotein, which facilitates the rapid generation of an immunological defense against damage caused by inflammation (Ceciliani & Pocacqua 2007).…”

“…Activated leukocytes may also act as a local source of α-1-acid glycoprotein, which facilitates the rapid generation of an immunological defense against damage caused by inflammation (Ceciliani & Pocacqua 2007).…”

Veterinary Biomarker Discovery: Proteomic Analysis of Acute Phase Proteins

“…Similar to the PTM of HPT, glycosylation of AGP is also altered during animal diseases. During inflammation, increases in plasma concentrations of AGP, as well as many structural modifications including the glycoslyation pattern and the degree of branching and fucosylation of AGP have been reported (Ceceliani et al, 2007). The structure of the glycoprotein AGP has been analyzed in several species including cows, sheep and rats, with the results indicating that the glycosylation pattern of AGP was quite variable (Nakano et al, 2004).…”

Alpha-1-Acid Glycoprotein (AGP) as a Potential Biomarker for Breast Cancer

“…Alpha -1 (or 1) -acid glycoprotein (AGP, or orosomucoid) is an important example of a naturally occurring N-linked plasma glycoprotein secreted by liver parenchymal cells. It was first isolated and characterised in the 1950s and although its specific biological role/function has yet to be clearly defined it is considered a natural anti-inflammatory and immunomodulatory agent [7][8][9], the concentration and/or 'normal' glycosylation of which may change under various physiological and pathophysiological conditions. It is a highly glycosylated (45%) protein and therefore investigations into alterations in its glycan profile during different diseases has been, and is still, of great interest (Figure 1).…”