Back to Search
Start Over
Endogenous airway mucins carry glycans that bind Siglec-F and induce eosinophil apoptosis
- Source :
- Journal of Allergy and Clinical Immunology. 135:1329-1340.e9
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Background Sialic acid–binding, immunoglobulin-like lectin (Siglec) F is a glycan-binding protein selectively expressed on mouse eosinophils. Its engagement induces apoptosis, suggesting a pathway for ameliorating eosinophilia in the setting of asthma and other eosinophil-associated diseases. Siglec-F recognizes sialylated sulfated glycans in glycan-binding assays, but the identities of endogenous sialoside ligands and their glycoprotein carriers in vivo are unknown. Objectives To use mouse lung-derived materials to isolate, biochemically identify, and biologically characterize naturally occurring endogenous glycan ligands for Siglec-F. Methods Lungs from normal and mucin-deficient mice, as well as mouse tracheal epithelial cells, were investigated in vitro and in vivo for the expression of Siglec-F ligands. Western blotting and cytochemistry used Siglec-F-Fc as a probe for directed purification, followed by liquid chromatography–tandem mass spectrometry of recognized glycoproteins. Purified components were tested in mouse eosinophil-binding assays and flow cytometry–based cell death assays. Results We detected mouse lung glycoproteins that bound to Siglec-F; binding was sialic acid dependent. Proteomic analysis of Siglec-F binding material identified Muc5b and Muc4. Cross-affinity enrichment and histochemical analysis of lungs from mucin-deficient mice assigned and validated the identity of Muc5b as one glycoprotein ligand for Siglec-F. Purified mucin preparations carried sialylated and sulfated glycans, bound to eosinophils and induced their death in vitro . Mice conditionally deficient in Muc5b displayed exaggerated eosinophilic inflammation in response to intratracheal installation of IL-13. Conclusions These data identify a previously unrecognized endogenous anti-inflammatory property of airway mucins by which their glycans can control lung eosinophilia through engagement of Siglec-F.
- Subjects :
- Proteomics
Glycan
Immunology
Antigens, Differentiation, Myelomonocytic
Apoptosis
Mice, Transgenic
Plasma protein binding
Ligands
Article
Immunophenotyping
Mice
chemistry.chemical_compound
Polysaccharides
Animals
Immunology and Allergy
Sialic Acid Binding Immunoglobulin-like Lectins
Lung
chemistry.chemical_classification
Mucin-4
biology
Mucin
Mucins
SIGLEC
Lectin
Epithelial Cells
respiratory system
Mucin-5B
Molecular biology
Sialic acid
Eosinophils
Phenotype
chemistry
Biochemistry
biology.protein
Cytokines
Carrier Proteins
Glycoprotein
Protein Binding
Subjects
Details
- ISSN :
- 00916749
- Volume :
- 135
- Database :
- OpenAIRE
- Journal :
- Journal of Allergy and Clinical Immunology
- Accession number :
- edsair.doi.dedup.....f98f70f0f38cbbc673d7fcb723f5d0a3