Characterization of Expression of Glycan Ligands for Siglec-F in Normal Mouse Lungs

Guo, Jin; Brummet, Mary; Myers, Allen C.; Na, Ho Jeong; Rowland, Elizabeth A.; Schnaar, Ronald L.; Zheng, Tao; Zhu, Zhou; Bochner, Bruce S.

doi:10.1165/rcmb.2010-0007oc

Cited by 27 publications

(40 citation statements)

References 34 publications

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Section: Lung Inflammatory Diseasesmentioning

confidence: 97%

“…Although this specificity is shared with Siglec-F, this mouse paralog also binds with lower affinity to ligands without the sulfate 13, 56, 62–65 . In mouse models of ovalbumin-induced airway inflammation, Siglec-F ligands are dramatically upregulated on epithelial cells and mucins 62, 65–68 . In most, but not all, models of lung allergy, mice deficient in either Siglec-F or its ligands (for example ST3Gal3 −/− mice) exhibit strongly enhanced eosinophil infiltration 62, 67–69 .…”

Section: Lung Inflammatory Diseasesmentioning

confidence: 97%

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Siglec-mediated regulation of immune cell function in disease

2014

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All mammalian cells display a diverse array of glycan structures that differ from those found on microbial pathogens. Siglecs are a family of sialic acid-binding immunoglobulin-like receptors that participate in the discrimination of ‘self’ and ‘non-self’ and regulate the functions of cells in the innate and adaptive immune systems through recognition of their glycan ligands. In this review, we describe the recent advances in our understanding of the roles of Siglecs in the regulation of immune cell functions in infectious diseases, inflammation, neurodegeneration, autoimmune diseases and cancer.

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Section: Lung Inflammatory Diseasesmentioning

confidence: 97%

Section: Lung Inflammatory Diseasesmentioning

confidence: 97%

Siglec-mediated regulation of immune cell function in disease

2014

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“…For example, administration of Siglec-F antibodies in mouse models of chronic allergic asthma nearly normalizes eosinophilic pulmonary inflammatory responses and virtually eliminates lung remodeling [32,40 ■ ]. Siglec-F deficient mice, as well as mice deficient in a key enzyme required to synthesize its sialylated glycan ligands, namely the α2–3 sialyltransferase ST3Gal-III, display a selective enhancement of allergic eosinophilic inflammation [41-45], suggesting that the loss of specific sialic acids from lung glycoproteins allows the augmented accumulation and survival of eosinophils in the airways of these mice. Proteomic analysis of Siglec-F binding material enriched from mouse lungs or mouse airway cells grown in vitro identified Muc5b and Muc4 as carriers of sialylated glycan ligands for Siglec-F. Muc5b-deficient mice exhibited decreased Siglec-F-Fc binding to their airways, most consistently in airway submucosal glands.…”

Section: Introductionmentioning

confidence: 99%

Regulation of airway inflammation by Siglec-8 and Siglec-9 sialoglycan ligand expression

Schleimer

Schnaar

Bochner

2016

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review Inflammatory cells involved in the allergic response, including eosinophils, mast cells, basophils, and neutrophils, express sialoglycan-binding proteins such as Siglec-8 and Siglec-9, which inhibit cell function and survival. The purpose of this review is to briefly discuss the biology of these siglecs and their ligands and consider their potential impact in pathology and treatment of chronic rhinosinusitis (CRS). Recent findings Recent studies demonstrate the presence of ligands for Siglec-8 and Siglec-9 in sinonasal tissue from patients with CRS as well as healthy patients, suggesting that the immunoregulatory functions of siglecs may be triggered in sinus tissue in health and disease. Summary Ligands for Siglec-8 and Siglec-9 may regulate the function of eosinophils, mast cells, neutrophils, and other cells in sinus mucosa. Therapeutic strategies that activate the anti-inflammatory effects of siglecs may dampen inflammation and disease in CRS patients.

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“…16, 30 Engagement of Siglec-8/-F or Siglec-9 with antibodies and/or artificial ligands in vitro cause eosinophil and neutrophil death, respectively (Figure 1). 23, 30–32 At least for Siglec-F, generation of these ligands in vivo requires the specific enzyme ST3Gal-III, an α2,3 sialyltransferase, and mice deficient in this enzyme lack lung ligands for Siglec-F. 33 In contrast, the presumed sulfotransferase required to generate the sulfation in 6′-sulfo-sialyl Lewis X, namely keratin sulfate galactose 6-O-sulfotransferase, is not required for generation of Siglec-F ligands, raising the possibility that endogenous ligands may not require sulfation to bind to Siglec-F. 34 The exact identity of these sialoside-carrying glycoprotein ligands for Siglec-F in the airways of mice and humans are actively under study, but at least for Siglec-F appear to include mucins such as Muc5b. 34, 35 …”

Section: Expression Patterns Ligands and Cellular Functions Of Selecmentioning

confidence: 99%

Role of siglecs and related glycan-binding proteins in immune responses and immunoregulation

Bochner

Zimmermann

2015

Journal of Allergy and Clinical Immunology

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Eukaryotic cells and extracellular material are heavily decorated by various glycans, yet the understanding of the structure and function of these moieties lags behind our understanding of nucleic acids, lipids and proteins. Recent years have seen a tremendous acceleration of understanding in the field of glycobiology, revealing many intricacies and functional contributions that were previously poorly understood or even unrecognized. This review highlights several topics relevant to glycoimmunology, where mammalian and pathogen-derived glycans displayed on glycoproteins and other scaffolds are recognized by specific glycan-binding proteins (GBPs), leading to a variety of pro- and anti-inflammatory cellular responses. The focus for this review is mainly on two families of GBPs, siglecs and selectins, that are involved in multiple steps of the immune response, including distinguishing pathogens from self, cell trafficking to sites of inflammation, fine-tuning of immune responses leading to activation or tolerance, and regulation of cell survival. Importantly for the clinician, accelerated rates of discovery in the field of glycoimmunology are being translated into innovative medicinal approaches that harness the interaction of glycans and GBPs to the benefit of the host, and may soon lead to novel diagnostics and therapeutics.

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Characterization of Expression of Glycan Ligands for Siglec-F in Normal Mouse Lungs

Cited by 27 publications

References 34 publications

Siglec-mediated regulation of immune cell function in disease

Siglec-mediated regulation of immune cell function in disease

Regulation of airway inflammation by Siglec-8 and Siglec-9 sialoglycan ligand expression

Role of siglecs and related glycan-binding proteins in immune responses and immunoregulation

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