Expression of ligands for Siglec-8 and Siglec-9 in human airways and airway cells - 05/03/15
Abstract |
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.
Conclusion |
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.
Le texte complet de cet article est disponible en PDF.Key words : Chronic rhinosinusitis, inflammation, submucosal gland cells, siglecs, glycobiology, mucin 5B, nuclear factor κB
Abbreviations used : Benzyl-α-GalNAc, CRS, ECL, GAPDH, HRP, ITIM, MUC5B, Neu5Ac2en, NF-κB, PBS, PBSTr, PBSTw, PVDF, siRNA
Plan
| Supported by the Lung Inflammatory Disease Program of Excellence in Glycoscience from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (P01 HL107151). R.P.S. was supported by R37 HL068546 and P01 AI106683 from the NIH and by the Ernest S. Bazley Foundation. A.G.-G. was supported in part by the NIH-funded Chemistry-Biology Interface Program at Johns Hopkins University (T32 GM080189). |
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| Disclosure of potential conflict of interest: A. Gonzalez-Gil has received research and travel support from the National Heart, Lung, and Blood Institute (NHLBI). W. W. Stevens has received research support from the National Institutes of Health (NIH). A. T. Peters has consultant arrangements with Greer Laboratories and has received payment for lectures from Baxter. B. S. Bochner has received research support from the NIH/NHLBI, has received a consulting fee or honorarium from Allakos, has patents regarding Siglec-8 and its ligand that belong to Johns Hopkins University, might receive royalties from Johns Hopkins University in the future regarding the sale of Siglec-8 products, and has stock/stock options with Allakos. R. P. Schleimer has received research support from the NIH; has consultant arrangements with Intersect ENT, GlaxoSmithKline, Allakos, Aurasense, and Merck; and has stock/stock options with Allakos, Aurasense, and BioMarck. R. L. Schnaar has received research support from the NIH/NHLBI and is coinventor of a patent related to Siglec-8 ligand structure (US patent 7,745,421). The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 135 - N° 3
P. 799 - mars 2015 Retour au numéro
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