α₁-Acid Glycoprotein

Abstract

α₁ -Acid glycoprotein (AGP) is a heavily glycosylated serum glycoprotein containing five complex-type N-linked glycans (Fig. 1) [1,2]. It is a positive acute-phase glycoprotein of which the plasma level will increase 2-6-fold under acute (e.g. trauma, burns, bacterial infections) or chronic inflammatory conditions (e.g. rheumatoid arthritis (RA)) as a result of the hepatic acute-phase reaction. Its exact function is not known yet, although drug- and steroid-binding activities have been described [3,4], but also a number of immunomodulating activities [5–8]. The latter activities have appeared to depend on the carbohydrate moiety of the molecule. At least 12 glycoforms of AGP can be detected in normal serum [9]. They differ in degree of branching (di-antennary versus tri- or tetraantennary glycans) as well as in degree of fucosylation and sialylation of the glycans. Formerly, it was assumed that the occurrence of these glycoforms resulted from a non-specific heterogeneity in the glycosylation process of AGP during its biosynthesis in the liver. However, in the last decade this view has changed, because it has become clear that the relative occurrence of the AGP glycoforms in plasma is strongly dependent on the (patho) physiological condition. For example, acute inflammation induces transient time-dependent increases in the level of diantennary containing glycoforms, coinciding partially with abundant increases of strongly fucosylated glycoforms of AGP [10]. Inflammatory cytokines and hormones are involved in the regulation of these changes by an, as yet, unknown effect on the glycosylation process in the liver [11]. This knowledge has become available owing to the technique developed by Bøg-Hansen [12] of crossed affmo-immunoelectrophoresis (CAIE) of sera or cell culture media with lectins as affino-component in the first dimension gel.