Human synovial lubricin expresses sialyl Lewis x determinant and has L-selectin ligand activity.

Abstract

Lubricin (or proteoglycan 4 (PRG4)) is an abundant mucin-like glycoprotein in synovial fluid (SF) and a major component responsible for joint lubrication. In this study, it was shown that O-linked core 2 oligosaccharides (Galβ1-3(GlcNAcβ1-6)GalNAcα1-Thr/Ser) on lubricin isolated from rheumatoid arthritis SF contained both sulfate and fucose residues, and SF lubricin was capable of binding to recombinant L-selectin in a glycosylation-dependent manner. Using resting human polymorphonuclear granulocytes (PMN) from peripheral blood, confocal microscopy showed that lubricin coated circulating PMN and that it partly co-localized with L-selectin expressed by these cells. In agreement with this, activation-induced shedding of L-selectin also mediated decreased lubricin binding to PMN. It was also found that PMN recruited to inflamed synovial area and fluid in rheumatoid arthritis patients kept a coat of lubricin. These observations suggest that lubricin is able to bind to PMN via an L-selectin-dependent and -independent manner and may play a role in PMN-mediated inflammation.

• Authors: Chunsheng Jin, Anna-Karin Hultgård Ekwall, Johan Bylund, Lena Björkman, Ruby P Estrella, John M Whitelock, Thomas Eisler, Maria Bokarewa, Niclas G Karlsson
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 43 Pg. 35922-33 (Oct 19 2012) ISSN: 1083-351X [Electronic] United States
• PMID: 22930755 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycoproteins
• Lewis Blood Group Antigens
• Lewis a oligosaccharide
• Oligosaccharides
• PRG4 protein, human
• Proteoglycans
• lubricin
• L-Selectin

Topics

• Adult
• Aged
• Arthritis, Rheumatoid (metabolism, pathology)
• Female
• Glycoproteins (metabolism)
• Humans
• Inflammation (metabolism, pathology)
• L-Selectin (biosynthesis)
• Leukocytes, Mononuclear (metabolism, pathology)
• Lewis Blood Group Antigens
• Male
• Middle Aged
• Oligosaccharides (metabolism)
• Protein Binding
• Proteoglycans (metabolism)
• Synovial Fluid (metabolism)