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.
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Abbreviations
- FcRn:
-
Human neonatal Fc receptor
- ß2m:
-
beta2-Microglobulin
- DAPI:
-
4′,6-diamidino-2-phenylindole, dihydrochloride
- PBS:
-
Phosphate-buffered saline
- EEA1:
-
Early endosomal antigen-1
- LAMP-2:
-
Lysosomal associated membrane protein-2.
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Acknowledgments
The skillful technical assistance of Katharina Gelles in tissue embedding and staining is greatly acknowledged. Supported by Jubiläumsfondsprojekt 8010 to I.E and Austrian Science Fund W1248-B13 to V.N.
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Heidl, S., Ellinger, I., Niederberger, V. et al. Localization of the human neonatal Fc receptor (FcRn) in human nasal epithelium. Protoplasma 253, 1557–1564 (2016). https://doi.org/10.1007/s00709-015-0918-y
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DOI: https://doi.org/10.1007/s00709-015-0918-y