Expression and transport functionality of FcRn within rat alveolar epithelium:A study in primary cell culture and in the isolated perfused lung

Sakagami, Masahiro, Omidi, Yadollah, Campbell, Lee, Kandalaft, Lana E., Morris, Christopher J. ORCID: https://orcid.org/0000-0002-7703-4474, Barar, Jaleh and Gumbleton, Mark (2006) Expression and transport functionality of FcRn within rat alveolar epithelium:A study in primary cell culture and in the isolated perfused lung. Pharmaceutical Research, 23 (2). pp. 270-279. ISSN 0724-8741

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Abstract

* Purpose. The neonatal constant region fragment receptor (FcRn) binds and transports IgG. FcRn expression in the upper tracheobronchial airways of the lung is recognized. In this study, we sought to characterize the functional expression of FcRn within alveolar regions of lung tissue. * Methods. FcRn immunohistochemistry was performed on intact rat lung. FcRn expression [Western blot, reverse transcription-polymerase chain reaction (RT-PCR), and immunofluorescence microscopy] and IgG transport functionality were assessed in an in vitro rat alveolar epithelial primary cell culture model. An isolated perfused rat lung model was used to examine IgG transport across pulmonary epithelium from airspace to perfusate. * Results. FcRn is expressed in intact alveolar epithelium, substantiated by expression and functionality in an in vitro alveolar epithelial model within which IgG transport was temperature sensitive, concentration dependent, and inhibited by excess unlabeled IgG and, to a disproportionate level, by anti-FcRn antibody. Saturable IgG transport across pulmonary epithelium was evident in an isolated perfused rat lung, inhibitable by competing IgG, and displayed a relatively low maximal net IgG absorptive rate of approximately 80 ng/h. * Conclusion. Pulmonary epithelium expresses functional FcRn providing an absorption pathway potentially important for highly potent Fcγ-fusion proteins but unlikely to be of quantitative significance for the systemic delivery of inhaled therapeutic monoclonal IgGs.

Item Type: Article
Additional Information: Funding Information: The authors are grateful to Pamela J. Björkman, Ph.D., Division of Biology, California Institute of Technology, Pasadena, CA, USA, for her gift of truncated rFcRn. This research began during MS’s 2-month research leave at Cardiff University (CU) and was supported in part by the Medical College of Virginia Foundation, Richmond, VA, USA, and by MG’s research funds at Cardiff University, UK. MS and MG acknowledge the encouragement of Peter Byron, Ph.D., School of Pharmacy Virginia Commonwealth University, throughout this work.
Uncontrolled Keywords: igg,isolated perfused lung,lung,neonatal constant region fragment receptor (fcrn),transport,biotechnology,molecular medicine,pharmacology,pharmaceutical science,organic chemistry,pharmacology (medical) ,/dk/atira/pure/subjectarea/asjc/1300/1305
Faculty \ School: Faculty of Science > School of Pharmacy
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Depositing User: LivePure Connector
Date Deposited: 19 Jul 2022 17:30
Last Modified: 13 Aug 2022 02:26
URI: https://ueaeprints.uea.ac.uk/id/eprint/86654
DOI: 10.1007/s11095-005-9226-0

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