α1-Acid Glycoprotein (AGP) is a glycoprotein which increases in
concentration in the plasma two to five folds in humans (but also ten to twenty folds in
some animals) as a consequence of the systemic response to the inflammation, the so
called acute phase reaction. The protein exposes on its surface five N-linked glycans,
which exhibit a high degree of subtle structural variations resulting in the expression in
blood of several isoforms which have identical amino acid sequence, but different
glycosylation patterns. The relative occurrence of these glycoforms are strictly
dependent on the pathophysiological status, that is determined by cytokines and
hormones produced during inflammation.
Both cytokines and hormones induce changes in the post-translational modification of
the protein, and these modifications are independent on the rate of synthesis of the
AGP. This review will be subdivided in two parts. The first part will describe the
structure of AGP (amino acid sequence and glycan pattern) and the several biological
functions identified so far for this protein. The second part will be devoted to the posttranslational
modifications of the glycan pattern of AGP due to pathological states,
since one of the most interesting features of AGP is that its oligosaccharides microheterogeneity
is profoundly affected by pathologic conditions and different glycoforms
can appear in plasma during systemic inflammation or diseases.
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 will also be discussed.
Keywords: Glycosylation, sialic acid, innate immunity, post-translational
modification, alpha 1 acid glycoprotein, acute phase reaction, inflammation,
apoptosis, proteins, carbohydrates, chemotaxis.
