Pharmaceutical Research

, Volume 23, Issue 2, pp 270–279 | Cite as

Expression and Transport Functionality of FcRn within Rat Alveolar Epithelium: A Study in Primary Cell Culture and in the Isolated Perfused Lung

  • Masahiro Sakagami
  • Yadollah Omidi
  • Lee Campbell
  • Lana E. Kandalaft
  • Christopher J. Morris
  • Jaleh Barar
  • Mark Gumbleton
Research Paper


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.


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.


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.


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.

Key Words

IgG isolated perfused lung lung neonatal constant region fragment receptor (FcRn) transport 



alveolar epithelial


bovine serum albumin


complementary deoxyribonucleic acid


Dulbecco's modified Eagle medium


ethylenediaminetetraacetic acid


enzyme-linked immunosorbent assay


fetal bovine serum


neonatal Fc receptor


fluorescein isothiocyanate


horseradish peroxide


immunoglobulin G


isolated perfused rat lung


metered dose inhaler


major histocompatibility complex


molecular weight cutoff


National Institute of Health


reverse transcriptase


reverse transcription–polymerase chain reaction


sodium dodecyl sulfate–polyacrylamide gel electrophoresis


Tris-buffered saline with Tween 20


total RNA





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.


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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Masahiro Sakagami
    • 1
  • Yadollah Omidi
    • 2
    • 3
  • Lee Campbell
    • 2
  • Lana E. Kandalaft
    • 2
  • Christopher J. Morris
    • 2
  • Jaleh Barar
    • 2
    • 3
  • Mark Gumbleton
    • 2
  1. 1.Department of Pharmaceutics, School of PharmacyVirginia Commonwealth UniversityRichmondUSA
  2. 2.Pharmaceutical Cell Biology, Welsh School of PharmacyCardiff UniversityCardiffUK
  3. 3.Faculty of PharmacyTabriz University of Medical SciencesTabrizIran

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