title: Localization of the human neonatal Fc receptor (FcRn) in human nasal epithelium.
abstract: The airway epithelium is a central player in the defense against pathogens including efficient mucociliary clearance and secretion of immunoglobulins, mainly polymeric IgA, but also IgG. Pulmonary administration of therapeutic antibodies on one hand, and intranasal immunization on the other, are powerful tools to treat airway infections. In either case, the airway epithelium is the primary site of antibody transfer. In various epithelia, bi-polar transcytosis of IgG and IgG immune complexes is mediated by the human neonatal Fc receptor, FcRn, but FcRn expression in the nasal epithelium had not been demonstrated, so far. We prepared affinity-purified antibodies against FcRn α-chain and confirmed their specificity by Western blotting and immunofluorescence microscopy. These antibodies were used to study the localization of FcRn α-chain in fixed nasal tissue. We here demonstrate for the first time that ciliated epithelial cells, basal cells, gland cells, and endothelial cells in the underlying connective tissue express the receptor. A predominant basolateral steady state distribution of the receptor was observed in ciliated epithelial as well as in gland cells. Co-localization of FcRn α-chain with IgG or with early sorting endosomes (EEA1-positive) but not with late endosomes/lysosomes (LAMP-2-positive) in ciliated cells was observed. This is indicative for the presence of the receptor in the recycling/transcytotic pathway but not in compartments involved in lysosomal degradation supporting the role of FcRn in IgG transcytosis in the nasal epithelium.
authors.affiliation: Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: Sara
authors.initials: S
authors.lastname: Heidl
authors.affiliation: Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: Isabella
authors.initials: I
authors.lastname: Ellinger
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria.
authors.forename: Verena
authors.initials: V
authors.lastname: Niederberger
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria.
authors.forename: Eva E
authors.initials: EE
authors.lastname: Waltl
authors.affiliation: Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. renate.fuchs@meduniwien.ac.at.
authors.forename: Renate
authors.initials: R
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport; D011817:Rabbits; D011961:Receptors, Fc / Q000378:metabolism*
chemical_list: D000906:Antibodies; D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; C100688:Fc receptor, neonatal
keywords: Immunoglobulin G; Nasal mucosa; Neonatal Fc receptor