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Effects of α1‐acid Glycoprotein Fucosylation on its Ca 2+ Mobilizing Capacity in Neutrophils
Author(s) -
Levander L.,
Gunnarsson P.,
Grenegård M.,
Rydén I.,
Påhlsson P.
Publication year - 2009
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2009.02240.x
Subject(s) - fucosylation , sialic acid , glycoconjugate , glycoprotein , chemistry , oligosaccharide , fucose , biochemistry , epitope , fucosyltransferase , siglec , inflammation , receptor , immunology , antigen , biology , enzyme
We recently showed that the acute‐phase protein α 1 ‐acid glycoprotein (AGP) induces rises in cytosolic calcium concentration, [Ca 2+ ] i, in neutrophils through sialic acid dependent interactions with the neutrophil receptors siglec‐5 and/or siglec‐14. Whereas both siglec‐5 and siglec‐14 have a relatively broad specificity for sialylated oligosaccharide structures, including both structures with terminal α2–3 or α2–6 linked sialic acid, there is a markedly reduced affinity to the fucosylated epitope sialyl Lewis x (SLe x ). Increased fucosylation, leading to increased expression of SLe x on AGP is commonly associated with inflammatory conditions. In the present study, we investigated whether an increased SLe x expression would affect the Ca 2+ ‐mobilizing effect of AGP. AGP with elevated fucose content isolated from patients with untreated chronic joint inflammation showed a decreased [Ca 2+ ] i modulatory effect on neutrophils compared to normally fucosylated AGP. Furthermore a hyperfucosylated AGP form produced by in vitro fucosylation, that consequently had an elevated expression of SLe x , could not elicit a [Ca 2+ ] i increase in neutrophils. The role of the carbohydrate portion of AGP in modulating neutrophil responses was further strengthened by showing that synthetic glycoconjugates carrying oligosaccharides with terminal α2–3 or α2–6 linked sialic acid were able to mimic the Ca 2+ ‐mobilizing effect of AGP whereas a synthetic glycoconjugate carrying SLe x was not. Based on these data, we conclude that increased fucosylation can alter the ability of AGP to induce neutrophil signalling and further supports an important role of the oligosaccharide chains of AGP in the modulation of leukocyte functions during an inflammatory process.