Impact of Glycosylation and Species Origin on the Uptake and Permeation of IgGs through the Nasal Airway Mucosa

Autor:	Johannes Flamm, Boris Mizaikoff, Rebecca Hermann, Patrick Schlossbauer, Simone Ladel, Alina Handl, Helena Herzog, Thomas Hummel, Frank Maigler, Katharina Schindowski
Rok vydání:	2020
Předmět:	Glycosylation Respiratory mucosa Pharmaceutical Science primary cells Mucous membrane of nose Article respiratory epithelium 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neonatal Fc receptor RPMI 2650 Olfactory mucosa barrier model medicine IgG permeation ddc:610 Receptor Immunglobulin G 030304 developmental biology 0303 health sciences Chemistry Permeation blood-brain barrier Riechepithel Molecular biology medicine.anatomical_structure Immunoglobulin G 030220 oncology & carcinogenesis drug delivery Respiratory epithelium Nasal administration nose-to-brain olfactory epithelium DDC 610 / Medicine & health Olfactory epithelium Ex vivo
Zdroj:	Pharmaceutics Volume 12 Issue 11
ISSN:	1999-4923
DOI:	10.3390/pharmaceutics12111014
Popis:	Although we have recently reported the involvement of neonatal Fc receptor (FcRn) in intranasal transport, the transport mechanisms are far from being elucidated. Ex vivo porcine olfactory tissue, primary cells from porcine olfactory epithelium (OEPC) and the human cell line RPMI 2650 were used to evaluate the permeation of porcine and human IgG antibodies through the nasal mucosa. IgGs were used in their wild type and deglycosylated form to investigate the impact of glycosylation. Further, the expression of FcRn and Fc-gamma receptor (FCGR) and their interaction with IgG were analyzed. Comparable permeation rates for human and porcine IgG were observed in OEPC, which display the highest expression of FcRn. Only traces of porcine IgGs could be recovered at the basolateral compartment in ex vivo olfactory tissue, while human IgGs reached far higher levels. Deglycosylated human IgG showed significantly higher permeation in comparison to the wild type in RPMI 2650 and OEPC, but insignificantly elevated in the ex vivo model. An immunoprecipitation with porcine primary cells and tissue identified FCGR2 as a potential interaction partner in the nasal mucosa. Glycosylation sensitive receptors appear to be involved in the uptake, transport, but also degradation of therapeutic IgGs in the airway epithelial layer. publishedVersion
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::924426981c0f304b3dfe1f12c561bffc https://doi.org/10.3390/pharmaceutics12111014 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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