PMID- 33755113 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20220531 IS - 1460-2423 (Electronic) IS - 0959-6658 (Print) IS - 0959-6658 (Linking) VI - 31 IP - 8 DP - 2021 Sep 9 TI - Induction of the endogenous sialoglycan ligand for eosinophil death receptor Siglec-8 in chronic rhinosinusitis with hyperplastic nasal polyposis. PG - 1026-1036 LID - 10.1093/glycob/cwab018 [doi] AB - Siglec-8, an immune-inhibitory sialoglycan binding lectin (S8), is expressed on the surface of eosinophils and mast cells, which are potent mediators of allergic inflammation. When S8 engages endogenous sialoglycan ligands, eosinophils undergo apoptosis and mast cell mediator release is inhibited. In the human airway, Siglec-8 ligands (S8L) are sialylated keratan sulfate chains carried on isoforms of the protein Deleted in Malignant Brain Tumors-1 (DMBT1), an immunoregulatory protein that we recently identified as the endogenous ligand for S8, DMBT1S8. We herein report that S8L is overexpressed in chronic rhinosinusitis with nasal polyposis (CRSwNP), a prevalent eosinophilic laden airway disease. Quantification and comparison of the degree to which DMBT1 carries the S8L by immunoblot analysis and lectin blot overlay, respectively, from nasal lavage showed that the S8L/DMBT1 ratio was significantly increased in CRSwNP vs. control or CRS patients. We identified the histological sites of S8L and DMBT1 expression in fresh surgically resected human nasal polyps. Histochemistry of diseased polyps and adjacent nondiseased middle turbinate (MT) tissue from CRSwNP demonstrated colocalization of S8L and DMBT1 with highest staining in submucosal glands >> epithelium > stoma. S8L expression was specifically elevated in the submucosal glands and epithelium of polyp tissue compared to MT. We hypothesize that expression of the isoform of DMBT1 carrying the Siglec-8 binding sialoglycan, DMBT1S8, is induced in polyps of CRSwNP specifically at the site of disease, is produced in the submucosal glands of polyps and secreted into the lumen of the sinonasal cavity as a host response to mitigate eosinophil-mediated inflammation. CI - (c) The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Lee, Hyun Sil AU - Lee HS AD - Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. FAU - Gonzalez-Gil, Anabel AU - Gonzalez-Gil A AD - Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. FAU - Drake, Virginia AU - Drake V AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. FAU - Li, T August AU - Li TA AD - Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. FAU - Schnaar, Ronald L AU - Schnaar RL AD - Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. FAU - Kim, Jean AU - Kim J AD - Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. LA - eng GR - K12 HL141952/NH/NIH HHS/United States GR - U19 AI136443/AI/NIAID NIH HHS/United States GR - K12 HL141952/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Glycobiology JT - Glycobiology JID - 9104124 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, B-Lymphocyte) RN - 0 (Calcium-Binding Proteins) RN - 0 (DMBT1 protein, human) RN - 0 (DNA-Binding Proteins) RN - 0 (Lectins) RN - 0 (Ligands) RN - 0 (Receptors, Death Domain) RN - 0 (SIGLEC8 protein, human) RN - 0 (Sialic Acid Binding Immunoglobulin-like Lectins) RN - 0 (Tumor Suppressor Proteins) SB - IM MH - Antigens, CD/*metabolism MH - Antigens, Differentiation, B-Lymphocyte/*metabolism MH - Calcium-Binding Proteins/metabolism MH - DNA-Binding Proteins MH - Eosinophils/metabolism MH - Humans MH - Lectins/*metabolism MH - Ligands MH - *Nasal Polyps/metabolism/pathology MH - Receptors, Death Domain/metabolism MH - *Rhinitis/metabolism/pathology MH - *Sialic Acid Binding Immunoglobulin-like Lectins/metabolism MH - Tumor Suppressor Proteins/metabolism PMC - PMC8434800 OTO - NOTNLM OT - Siglec-8 ligand OT - Type 2 inflammation OT - chronic rhinosinusitis with nasal polyposis OT - deleted in malignant brain tumors-1 OT - eosinophilic nasal polyps EDAT- 2021/03/24 06:00 MHDA- 2022/04/01 06:00 PMCR- 2022/03/20 CRDT- 2021/03/23 12:30 PHST- 2020/08/21 00:00 [received] PHST- 2021/02/15 00:00 [revised] PHST- 2021/03/01 00:00 [accepted] PHST- 2021/03/24 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2021/03/23 12:30 [entrez] PHST- 2022/03/20 00:00 [pmc-release] AID - 6179196 [pii] AID - cwab018 [pii] AID - 10.1093/glycob/cwab018 [doi] PST - ppublish SO - Glycobiology. 2021 Sep 9;31(8):1026-1036. doi: 10.1093/glycob/cwab018.