Characterization of the interactions of rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG isotypes

Despite the increasing importance of rabbit as an animal model in pharmacological studies like investigating placental transfer of therapeutic IgGs, little is known about the molecular interaction of the rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG molecules. We analyzed the interact...

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Autores principales: Szikora, Bence, Hiripi, László, Bender, Balázs, Kacskovics, Imre, Iliás, Attila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619814/
https://www.ncbi.nlm.nih.gov/pubmed/28957416
http://dx.doi.org/10.1371/journal.pone.0185662
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author Szikora, Bence
Hiripi, László
Bender, Balázs
Kacskovics, Imre
Iliás, Attila
author_facet Szikora, Bence
Hiripi, László
Bender, Balázs
Kacskovics, Imre
Iliás, Attila
author_sort Szikora, Bence
collection PubMed
description Despite the increasing importance of rabbit as an animal model in pharmacological studies like investigating placental transfer of therapeutic IgGs, little is known about the molecular interaction of the rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG molecules. We analyzed the interactions of the rabbit and human FcRn with rabbit and human IgG isotypes using surface plasmon resonance assay. Similar to FcRn of other species, rabbit FcRn functions in pH-dependent manner, as it binds IgGs at pH 6.0, but no binding occurs at pH 7.4. We also showed that rabbit FcRn binds rabbit IgG and human IgG1 with nearly identical affinity, whereas it has stronger interactions with the other human IgG isotypes. The similar affinity of rabbit IgG and human IgG1 for rabbit FcRn was confirmed by in vitro FcRn-mediated recycling assay. These data verify that rabbit is an appropriate animal model for analyzing the pharmacokinetics of human therapeutic monoclonal antibodies.
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spelling pubmed-56198142017-10-17 Characterization of the interactions of rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG isotypes Szikora, Bence Hiripi, László Bender, Balázs Kacskovics, Imre Iliás, Attila PLoS One Research Article Despite the increasing importance of rabbit as an animal model in pharmacological studies like investigating placental transfer of therapeutic IgGs, little is known about the molecular interaction of the rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG molecules. We analyzed the interactions of the rabbit and human FcRn with rabbit and human IgG isotypes using surface plasmon resonance assay. Similar to FcRn of other species, rabbit FcRn functions in pH-dependent manner, as it binds IgGs at pH 6.0, but no binding occurs at pH 7.4. We also showed that rabbit FcRn binds rabbit IgG and human IgG1 with nearly identical affinity, whereas it has stronger interactions with the other human IgG isotypes. The similar affinity of rabbit IgG and human IgG1 for rabbit FcRn was confirmed by in vitro FcRn-mediated recycling assay. These data verify that rabbit is an appropriate animal model for analyzing the pharmacokinetics of human therapeutic monoclonal antibodies. Public Library of Science 2017-09-28 /pmc/articles/PMC5619814/ /pubmed/28957416 http://dx.doi.org/10.1371/journal.pone.0185662 Text en © 2017 Szikora et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Szikora, Bence
Hiripi, László
Bender, Balázs
Kacskovics, Imre
Iliás, Attila
Characterization of the interactions of rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG isotypes
title Characterization of the interactions of rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG isotypes
title_full Characterization of the interactions of rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG isotypes
title_fullStr Characterization of the interactions of rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG isotypes
title_full_unstemmed Characterization of the interactions of rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG isotypes
title_short Characterization of the interactions of rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG isotypes
title_sort characterization of the interactions of rabbit neonatal fc receptor (fcrn) with rabbit and human igg isotypes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619814/
https://www.ncbi.nlm.nih.gov/pubmed/28957416
http://dx.doi.org/10.1371/journal.pone.0185662
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