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

Abstract

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.

Glycobiology simplified: diverse roles of glycan recognition in inflammation

“…Siglec-8 and siglec-9 have the same domain architecture and share .65% amino acid sequence identity but are expressed on nonoverlapping subsets of leukocytes (Table 1) and bind to related, but nonoverlapping, glycans (Fig. Siglec-8 appears to function in resolving allergic inflammation [45], whereas siglec-9 may function in resolving neutrophil-mediated inflammation [53,54]. Siglec-8 appears to function in resolving allergic inflammation [45], whereas siglec-9 may function in resolving neutrophil-mediated inflammation [53,54].…”

“…8). Siglec-8 appears to function in resolving allergic inflammation [45], whereas siglec-9 may function in resolving neutrophil-mediated inflammation [53,54]. Evidence for function was obtained by clustering siglecs on the surfaces of human leukocytes using anti-siglec mAbs [55,56].…”

A Review of Classification Schemes for Chronic Rhinosinusitis with Nasal Polyposis Endotypes

“…Engaging the Siglec‐8 receptor has been shown to induce apoptosis of eosinophils and inhibition of mast cell degranulation. As such, ligands for Siglec‐8 have been suggested as a therapeutic strategy for suppressing sinonasal inflammation in eosinophil‐mediated CRSwNP …”

The modern trends in the diagnostic search for and the treatment of chronic rhinosinusitis with nasal polyps

“…Перспективным при эозинофильном CRSwNP может быть воздействие на трансмембранный ре цептор Siglec8, который экспрессируется на по верхности эозинофилов, базофилов и тучных клеток и относится к иммуноглобулиноподобным лекти нам, связывающим сиаловые кислоты. Связывание этого рецептора c синтетическим лигандом вызыва ет активацию митогенактивированных протеинки наз в эозинофилах, праймированных цитокинами, что приводит к их апоптозу [27]. В тучных клетках воздействие на Siglec8 ингибирует их дегрануля цию и выделение гистамина и простагландина D2, блокируя FcεRIрецептор [28].…”