Expression and Transport Functionality of FcRn within Rat Alveolar Epithelium: A Study in Primary Cell Culture and in the Isolated Perfused Lung
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- Sakagami, M., Omidi, Y., Campbell, L. et al. Pharm Res (2006) 23: 270. doi:10.1007/s11095-005-9226-0
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 WordsIgG isolated perfused lung lung neonatal constant region fragment receptor (FcRn) transport
bovine serum albumin
complementary deoxyribonucleic acid
Dulbecco's modified Eagle medium
enzyme-linked immunosorbent assay
fetal bovine serum
neonatal Fc receptor
isolated perfused rat lung
metered dose inhaler
major histocompatibility complex
molecular weight cutoff
National Institute of Health
reverse transcription–polymerase chain reaction
sodium dodecyl sulfate–polyacrylamide gel electrophoresis
Tris-buffered saline with Tween 20