ArticleThe Journal of allergy and clinical immunology2021
Isolation, identification, and characterization of the human airway ligand for the eosinophil and mast cell immunoinhibitory receptor Siglec-8.
Article in The Journal of allergy and clinical immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Predictions from deep learning propose substantial protein-carbohydrate interplay.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Understanding the Glycosylation Pathways Involved in the Biosynthesis of the Sulfated Glycan Ligands for Siglecs.ACS chemical biology · 2025Article
- Mast cells: key players in digestive system tumors and their interactions with immune cells.Cell death discovery · 2025Review
- Sialylated keratan sulfates on MUC5B are Siglec-8 ligands in the human esophagus.Glycobiology · 2024Article
- GlcNAc6ST2/CHST4 Is Essential for the Synthesis of R-10G-Reactive Keratan Sulfate/SulfatedMolecules (Basel, Switzerland) · 2024Article
- Siglecs as potential targets of therapy in human mast cell- and/or eosinophil-associated diseases.Seminars in immunology · 2023Review
- Siglecs in allergy and asthma.Molecular aspects of medicine · 2023Review
- Human sialoglycan ligands for immune inhibitory Siglecs.Molecular aspects of medicine · 2023Review
- (Glycan Binding) Activity-Based Protein Profiling in Cells Enabled by Mass Spectrometry-Based Proteomics.Israel journal of chemistry · 2023Article
- Reading the glyco-code: New approaches to studying protein-carbohydrate interactions.Current opinion in structural biology · 2022Review
- Complementary Role of GlcNAc6ST2 and GlcNAc6ST3 in Synthesis of CL40-Reactive Sialylated and Sulfated Glycans in the Mouse Pleural Mesothelium.Molecules (Basel, Switzerland) · 2022Article
- Human brain sialoglycan ligand for CD33, a microglial inhibitory Siglec implicated in Alzheimer's disease.The Journal of biological chemistry · 2022Article
- Induction of the endogenous sialoglycan ligand for eosinophil death receptor Siglec-8 in chronic rhinosinusitis with hyperplastic nasal polyposis.Glycobiology · 2021Article
- Rethinking neutrophils and eosinophils in chronic rhinosinusitis.The Journal of allergy and clinical immunology · 2021Review
- Siglec Ligands.Cells · 2021Review
- Recent Progress in the Methodologies to Identify Physiological Ligands of Siglecs.Frontiers in immunology · 2021Review
- Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe immunoinhibitory receptor Siglec-8 on the surface of human eosinophils and mast cells binds to sialic acid-containing ligands in the local milieu, resulting in eosinophil apoptosis, inhibition of mast cell degranulation, and suppression of inflammation. Siglec-8 ligands were found on postmortem human trachea and bronchi and on upper airways in 2 compartments, cartilage and submucosal glands, but they were surprisingly absent from the epithelium. We hypothesized that Siglec-8 ligands in submucosal glands and ducts are normally transported to the airway mucus layer, which is lost during tissue preparation.
objectiveOur aim was to identify the major Siglec-8 sialoglycan ligand on the mucus layer of human airways.
methodsHuman upper airway mucus layer proteins were recovered during presurgical nasal lavage of patients at a sinus clinic. Proteins were resolved by gel electrophoresis and blotted, and Siglec-8 ligands detected. Ligands were purified by size exclusion and affinity chromatography, identified by proteomic mass spectrometry, and validated by electrophoretic and histochemical colocalization. The affinity of Siglec-8 binding to purified human airway ligand was determined by inhibition of glycan binding.
resultsA Siglec-8-ligand with a molecular weight of approximately 1000 kDa was found in all patient nasal lavage samples. Purification and identification revealed deleted in malignant brain tumors 1 (DMBT1) (also known by the aliases GP340 and SALSA), a large glycoprotein with multiple O-glycosylation repeats. Immunoblotting, immunohistochemistry, and enzyme treatments confirmed that Siglec-8 ligand on the human airway mucus layer is an isoform of DMBT1 carrying O-linked sialylated keratan sulfate chains (DMBT1
conclusionA distinct DMBT1 isoform, DMBT1
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