title: The role of lung epithelial ligands for Siglec-8 and Siglec-F in eosinophilic inflammation.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21224-6821, USA.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kiwamoto
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Katoh
authors.forename: Michael
authors.initials: M
authors.lastname: Tiemeyer
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Bochner
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D001249:Asthma / Q000209:etiology*; D004804:Eosinophils / Q000502:physiology*; D006801:Humans; D037102:Lectins / Q000502:physiology*; D008024:Ligands; D008168:Lung / Q000502:physiology*; D051379:Mice; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D015214:Antigens, Differentiation, Myelomonocytic; D037102:Lectins; D008024:Ligands; C403967:SIGLEC8 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C443130:Siglecf protein, mouse