α1‐Acid Glycoprotein Derived from the Human Hepatoma Cell Line HepG2, and which Overexpresses Fucose, can Function as a Ligand for E‐selectin

α1-Acid glycoprotein (AGP) is an extensively glycosylated acute phase protein of uncertain physiological function. Nonetheless it may have immunomodulatory properties related to its oligosaccharide structures. Verification of the functional significance of glycosylation changes in AGP would be facilitated by the development of an appropriate in-vitro AGP production model capable, under certain conditions, of producing AGP with differing glycosylation patterns. The latter must reflect in-vivo glycosylation changes seen in inflammatory conditions. We have previously reported on the utility of the human hepatoma cell line, HepG2, as a crude model of inflammation-induced changes in AGP glycosylation. The monosaccharide composition of purified HepG2-derived AGP was qualitatively and quantitatively analysed by high pH anion-exchange chromatography. The oligosaccharides of the HepG2 AGP were found to overexpress fucose with respect to AGP purified from the pooled plasma of healthy subjects. The hypothesis that AGP, by virtue of sialyl Lewis X expression, may function to inhibit blood cell binding to the inflammation-induced endothelial adhesion molecule E-selectin was tested in a cell-protein binding assay. The HepG2-derived AGP was found to inhibit sialyl Lewis X-dependent cell adhesion to an immobilized E-selectin chimera in-vitro. These observations suggest that HepG2-derived AGP glycoforms may be of interest as model immunomodulators with respect to antagonizing sialyl Lewis X at E-selectin which could be the basis for a novel therapeutic entity. Further, overexpression of fucose is pivotal in this regard.