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

PurposeThe 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.MethodsFcRn 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.ResultsFcRn 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.ConclusionPulmonary 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.