Core 1-derived O-glycans are essential E-selectin ligands on neutrophils
| Autor: | Lijun Xia, J. Michael McDaniel, Tadayuki Yago, Jonathan J. Miner, Rodger P. McEver, Jianxin Fu |
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| Rok vydání: | 2010 |
| Předmět: |
Glycan
Neutrophils Glycoconjugate Sialoglycoproteins Ligands Mice Cell Movement Polysaccharides E-selectin Cell Adhesion Animals chemistry.chemical_classification Membrane Glycoproteins Multidisciplinary biology Reverse Transcriptase Polymerase Chain Reaction Mucin CD44 Biological Sciences Flow Cytometry Receptors Fibroblast Growth Factor Molecular biology In vitro Hyaluronan Receptors chemistry biology.protein E-Selectin Glycoprotein Selectin |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:9204-9209 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Neutrophils roll on E-selectin in inflamed venules through interactions with cell-surface glycoconjugates. The identification of physiologic E-selectin ligands on neutrophils has been elusive. Current evidence suggests that P-selectin glycoprotein ligand-1 (PSGL-1), E-selectin ligand-1 (ESL-1), and CD44 encompass all glycoprotein ligands for E-selectin; that ESL-1 and CD44 use N-glycans to bind to E-selectin; and that neutrophils lacking core 2 O-glycans have partially defective interactions with E-selectin. These data imply that N-glycans on ESL-1 and CD44 and O-glycans on PSGL-1 constitute all E-selectin ligands, with neither glycan subset having a dominant role. The enzyme T-synthase transfers Gal to GalNAcα1-Ser/Thr to form the core 1 structure Galβ1–3GalNAcα1-Ser/Thr, a precursor for core 2 and extended core 1 O-glycans that might serve as selectin ligands. Here, using mice lacking T-synthase in endothelial and hematopoietic cells, we found that E-selectin bound to CD44 and ESL-1 in lysates of T-synthase–deficient neutrophils. However, the cells exhibited markedly impaired rolling on E-selectin in vitro and in vivo, failed to activate β2 integrins while rolling, and did not emigrate into inflamed tissues. These defects were more severe than those of neutrophils lacking PSGL-1, CD44, and the mucin CD43. Our results demonstrate that core 1-derived O-glycans are essential E-selectin ligands; that some of these O-glycans are on protein(s) other than PSGL-1, CD44, and CD43; and that PSGL-1, CD44, and ESL-1 do not constitute all glycoprotein ligands for E-selectin. |
| Databáze: | OpenAIRE |
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