Siglec-8 and Siglec-9 binding specificities and endogenous airway ligand distributions and properties.

Abstract

Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression. In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release. Endogenous sialoglycan ligands in tissues, mostly uncharacterized, engage siglecs on leukocytes to inhibit inflammation. Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted. Since siglecs are involved in lung inflammation, we studied Siglec-8 and Siglec-9 ligands in human lungs and airways. Siglec-8 ligands are in tracheal submucosal glands and cartilage but not airway epithelium or connective tissues, whereas Siglec-9 ligands are broadly distributed. Mouse airways do not have Siglec-8 ligands, whereas Siglec-9 ligands are on airways of both species. Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested. Siglec-8 and Siglec-9 ligands in airways appear to be high molecular weight O-linked sialoglycoproteins. These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.

• Authors: Huifeng Yu, Anabel Gonzalez-Gil, Yadong Wei, Steve M Fernandes, Ryan N Porell, Katarina Vajn, James C Paulson, Corwin M Nycholat, Ronald L Schnaar
• Journal: Glycobiology (Glycobiology) Vol. 27 Issue 7 Pg. 657-668 (07 01 2017) ISSN: 1460-2423 [Electronic] England
• PMID: 28369504 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antigens, CD
• Antigens, Differentiation, B-Lymphocyte
• Lectins
• Ligands
• Polysaccharides
• SIGLEC8 protein, human
• SIGLEC9 protein, human
• Sialic Acid Binding Immunoglobulin-like Lectins
• N-Acetylneuraminic Acid

Topics

• Adult
• Antigens, CD (chemistry, metabolism)
• Antigens, Differentiation, B-Lymphocyte (chemistry, metabolism)
• Cells, Cultured
• Female
• Humans
• Lectins (chemistry, metabolism)
• Ligands
• Lung (cytology, metabolism)
• Male
• Middle Aged
• N-Acetylneuraminic Acid (metabolism)
• Polysaccharides (metabolism)
• Protein Binding
• Respiratory Mucosa (metabolism)
• Sialic Acid Binding Immunoglobulin-like Lectins (chemistry, metabolism)
• Trachea (cytology, metabolism)