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

Abstract

Pulmonary epithelium expresses functional FcRn providing an absorption pathway potentially important for highly potent Fcgamma-fusion proteins but unlikely to be of quantitative significance for the systemic delivery of inhaled therapeutic monoclonal IgGs.

Pegylation of Antimicrobial Peptides Maintains the Active Peptide Conformation, Model Membrane Interactions, and Antimicrobial Activity while Improving Lung Tissue Biocompatibility following Airway Delivery

“…Assessment of pulmonary barrier toxicity and AMP pulmonary absorption in an IPRL model. An IPRL preparation employing a forced intratracheal solution instillation technique was used as previously described (8,27,33). Briefly, a rat lung was surgically removed and housed horizontally in a humidified artificial glass thorax maintained at 37°C.…”

Systemic Delivery of Biotherapeutics Through the Lung: Opportunities and Challenges for Improved Lung Absorption

“…Thus, an innovative approach was attempted, exploiting the lung's transcytotic absorption mechanism via the neonatal constant fragment receptor (FcRn) to increase lung absorption of large proteins in a form of Fc-fusion molecules [46][47][48][49][50]. FcRn was identified as an Fc-binding receptor mediating absorptive transcytosis of IgG across the lung epithelium [51][52][53]. Thus, Fc-fusion proteins were prepared, yet as monomeric effector molecules rather than dimeric variants, to further increase the FcRn affinity and prolong the systemic half-life.…”

Neonatal Fc Receptor Mediates Internalization of Fc in Transfected Human Endothelial Cells

“…In addition, the fact that a relatively small fraction of the receptor is present on the cell surface (Borvak et al, 1998;Antohe et al, 2001;Spiekermann et al, 2002;Claypool et al, 2004;Stirling et al, 2005; This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-02-0101) on October 8, 2008. Sakagami et al, 2006) has been taken to suggest a limited potential for FcRn-mediated endocytosis of IgG. Because IgG is present in the serum at high concentrations (11-12 mg/ml in humans; Waldmann and Strober, 1969 and 1.5-8.0 mg/ml in mice; Ghetie et al, 1996;Telleman and Junghans 2000), fluid-phase internalization, particularly by endocytically active endothelial cells, could support a significant avenue of cellular internalization in vivo.…”