title: Glycosylation of site-specific glycans of alpha1-acid glycoprotein and alterations in acute and chronic inflammation.
abstract: BACKGROUND
  alpha(1)-Acid glycoprotein (AGP), an acute phase reactant, is extensively glycosylated at five Asn-linked glycosylation sites. In a number of pathophysiological states, including inflammation, rheumatoid arthritis, and cancer, alterations of Asn-linked glycans (N-glycans) have been reported. We investigated alteration of N-glycans at each of glycosylation sites of AGP in the sera of patients with acute and chronic inflammation.
  
  
  METHODS
  AGP purified from sera was digested with Glu-C and the liberated glycopeptides were isolated by reverse phase HPLC. N-glycans released with peptide N-glycosidase F and followed by neuraminidase treatment were analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry.
  
  
  RESULTS
  Site-specific differences in branching structures were observed among N-glycosylation sites 1, 3, 4 and 5. Within the sera of patients with acute inflammation, increases in bi-antennary and decreases in tri- and tetra-antennary structures were observed, as well as increases in alpha1,3-fucosylation, at most glycosylation sites. In the sera of patients with chronic inflammation, increased rates of tri-antennary alpha1,3-fucosylation at sites 3 and 4 and tetra-antennary alpha1,3-fucosylation at sites 3, 4 and 5 were detected. Although there were no significant differences between acute and chronic sera in site directed branching structures, significant differences of alpha1,3-fucosylation were detected in tri-antennary at sites 2, 4 and 5 and in tetra-antennary at sites 3 and 4.
  
  
  CONCLUSIONS
  Little variation in the N-glycan composition of the glycosylation sites of AGP was observed among healthy individuals, while the sera of patients with acute inflammation demonstrated increased numbers of bi-antennary and alpha1,3-fucosylated N-glycan structures at each glycosylation site.
authors.affiliation: Department of Clinical Chemistry, School of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274-8510, Japan. koji@phar.toho-u.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Higai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoki
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Azuma
authors.forename: Kojiro
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002908:Chronic Disease; D005643:Fucose / Q000378:metabolism; D006031:Glycosylation; D006041:Goats; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000378:metabolism* / Q000473:pathology; D008969:Molecular Sequence Data; D009961:Orosomucoid / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D009961:Orosomucoid; D005643:Fucose