title: 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.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA.
authors.forename: Anabel
authors.initials: A
authors.lastname: Gonzalez-Gil
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA.
authors.forename: Steve M
authors.initials: SM
authors.lastname: Fernandes
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA.
authors.forename: Ryan N
authors.initials: RN
authors.lastname: Porell
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA.
authors.forename: Katarina
authors.initials: K
authors.lastname: Vajn
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Corwin M
authors.initials: CM
authors.lastname: Nycholat
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Schnaar
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D020545:Respiratory Mucosa / Q000378:metabolism*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000737:chemistry / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D037102:Lectins; D008024:Ligands; D011134:Polysaccharides; C403967:SIGLEC8 protein, human; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D019158:N-Acetylneuraminic Acid
keywords: airways; sialic acid; siglec; submucosal glands; trachea