The role of lung epithelial ligands for Siglec-8 and Siglec-F in eosionophilic inflammation.

Kiwamoto, T., Katoh, T., Tiemeyer, M., Bochner,BS. (2013) The role of lung epithelial ligands for Siglec-8 and Siglec-F in eosionophilic inflammation. Curr Opin Allergy Clin Immunol. 13(1):106-11. PMID: 23160308

Abstract

PURPOSE OF REVIEW:

Siglec-8 and Siglec-F are single pass transmembrane inhibitory receptors found on the surface of human and mouse eosinophils, respectively, but very little is known about their physiologic glycan ligands. This article reviews the latest knowledge on this topic and outlines the strategies being used to further define the production and glycobiochemical nature of these molecules in the lung.

RECENT FINDINGS:

Both Siglec-8 and Siglec-F recognize the same glycan structure, namely 6′-sulfated sialyl Lewis X, as determined using glycan array technologies. Studies have identified α2,3-linked sialylated glycoprotein structures localized to mouse airway epithelium in tissue sections, where their constitutive expression requires the specific sialyltransferase St3gal3. Expression of these ligands in lung is enhanced during allergic inflammation and by cytokines such as IL-13, and is maintained in primary air-liquid interface cultures of mouse lung epithelium. Further characterization suggests that they are high molecular weight sialylated proteins, putatively mucins. By combining analytic glycomics, glycoproteomic mapping, and further in-vitro eosinophil experimentation including the ability of candidate structures to enhance eosinophil apoptosis, a finely detailed appreciation of the structural requirements for productive Siglec-8 and Siglec-F engagement should soon emerge.

SUMMARY:

An enhanced understanding of Siglec-F, Siglec-8, and their ligands should improve our understanding of endogenous lung pathways limiting the survival of eosinophils within the airway in diseases such as asthma. Knowledge of this biology may also result in novel opportunities for drug development involving glycans and glycomimetics that selectively bind to Siglec-8 and induce eosinophil death.

Link to journal: http://journals.lww.com/co-allergy/pages/default.aspx