Expression of ligands for Siglec-8 and Siglec-9 in human airways and airway cells.
BACKGROUND
Balanced activation and inhibition of the immune system ensures pathogen clearance while avoiding hyperinflammation. Siglecs, sialic acid-binding proteins found on subsets of immune cells, often inhibit inflammation: Siglec-8 on eosinophils and Siglec-9 on neutrophils engage sialoglycan ligands on airways to diminish ongoing inflammation. The identities of human siglec ligands and their expression during inflammation are largely unknown.


OBJECTIVE
The histologic distribution, expression, and molecular characteristics of siglec ligands were explored in healthy and inflamed human upper airways and in a cellular model of airway inflammation.


METHODS
Normal and chronically inflamed upper airway tissues were stained for siglec ligands. The ligands were extracted from normal and inflamed tissues and from human Calu-3 cells for quantitative analysis by means of siglec blotting and isolation by means of siglec capture.


RESULTS
Siglec-8 ligands were expressed on a subpopulation of submucosal gland cells of human inferior turbinate, whereas Siglec-9 ligands were expressed more broadly (submucosal glands, epithelium, and connective tissue); both were significantly upregulated in patients with chronic rhinosinusitis. Human airway (Calu-3) cells expressed Siglec-9 ligands on mucin 5B (MUC5B) under inflammatory control through the nuclear factor κB pathway, and MUC5B carried sialoglycan ligands of Siglec-9 on human upper airway tissue.


CONCLUSIONS
Inflammation results in upregulation of immune-inhibitory Siglec-8 and Siglec-9 sialoglycan ligands on human airways. Siglec-9 ligands are upregulated through the nuclear factor κB pathway, resulting in their enhanced expression on MUC5B. Siglec sialoglycan ligand expression in inflamed cells and tissues may contribute to the control of airway inflammation.
Department of Pharmacology, Third Military Medical University, Chongqing, China; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Md.
Yi
Y
Jia
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Md.
Huifeng
H
Yu
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Md.
Steve M
SM
Fernandes
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Md.
Yadong
Y
Wei
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Md.
Anabel
A
Gonzalez-Gil
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Md.
Mary G
MG
Motari
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Md.
Katarina
K
Vajn
Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Whitney W
WW
Stevens
Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Anju T
AT
Peters
Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Bruce S
BS
Bochner
Department of Otorhinolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Robert C
RC
Kern
Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Robert P
RP
Schleimer
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Md. Electronic address: schnaar@jhu.edu.
Ronald L
RL
Schnaar
D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D002908:Chronic Disease; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D037102:Lectins / Q000235:genetics* / Q000276:immunology; D008024:Ligands; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D055257:Mucin-5B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D012220:Rhinitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D012852:Sinusitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D037102:Lectins; D008024:Ligands; D008070:Lipopolysaccharides; C524578:MUC5B protein, human; D055257:Mucin-5B; D016328:NF-kappa B; D034741:RNA, Small Interfering; C403967:SIGLEC8 protein, human; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D014409:Tumor Necrosis Factor-alpha
Chronic rhinosinusitis; glycobiology; inflammation; mucin 5B; nuclear factor κB; siglecs; submucosal gland cells