Effects of alpha 1-acid Glycoprotein Fucosylation on its Ca2+ Mobilizing Capacity in Neutrophils
2009 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 69, no 5, 412-420 p.Article in journal (Refereed) Published
We recently showed that the acute-phase protein alpha(1)-acid glycoprotein (AGP) induces rises in cytosolic calcium concentration, [Ca2+](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 alpha 2-3 or alpha 2-6 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 Ca2+-mobilizing effect of AGP. AGP with elevated fucose content isolated from patients with untreated chronic joint inflammation showed a decreased [Ca2+](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 [Ca2+](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 alpha 2-3 or alpha 2-6 linked sialic acid were able to mimic the Ca2+-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.
Place, publisher, year, edition, pages
2009. Vol. 69, no 5, 412-420 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-18019DOI: 10.1111/j.1365-3083.2009.02240.xOAI: oai:DiVA.org:liu-18019DiVA: diva2:214257
On the day of the defence day the title of this article was "Increased fucosylation of α1‐acid glycoprotein decreases its Ca2+ mobilizing capacity in neutrophils".2009-05-042009-05-042014-01-16Bibliographically approved