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This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/L616    most recent 00121.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Kim, K.-J. Articles by Crandall, E. D. Search for Related Content PubMed PubMed Citation Articles by Kim, K.-J. Articles by Crandall, E. D.

Net absorption of IgG via FcRn-mediated transcytosis across rat alveolar epithelial cell monolayers

Departments of ¹Medicine, ²Physiology and Biophysics, ³Molecular Pharmacology and Toxicology, ⁵Biomedical Engineering, ⁶Pharmaceutical Sciences, ⁷Ophthalmology, ⁸Biochemistry and Molecular Biology, and ⁹Pathology, and ⁴Will Rogers Institute Pulmonary Research Center, Keck School of Medicine and Schools of Pharmacy and Engineering, University of Southern California, Los Angeles, California 90033

Submitted 1 April 2004 ; accepted in final form 19 May 2004

We characterized immunoglobulin G (IgG) transport across rat alveolar epithelial cell monolayers cultured on permeable supports. Unidirectional fluxes of biotin-labeled rat IgG (biot-rIgG) were measured in the apical-to-basolateral (ab) and opposite (ba) directions as functions of [rIgG] in upstream fluids at 37 and 4°C. We explored specificity of IgG transport by measuring fluxes in the presence of excess Fc, Fab, F(ab')₂, or chicken Ig (IgY). Expression of the IgG receptor FcRn and the effects of dexamethasone on FcRn expression and biot-rIgG fluxes were determined. Results show that ab flux of biot-rIgG is about fivefold greater than ba flux at an upstream concentration of 25 nM biot-rIgG at 37°C. Both ab and ba fluxes of rIgG saturate, resulting in net absorption with half-maximal concentration and maximal flow of 7.1 nM and 1.3 fmol·cm^–2·h^–1. At 4°C, both ab and ba fluxes significantly decrease, nearly collapsing net absorption. The presence of excess unlabeled Fc [but not Fab, F(ab')₂, or IgY] significantly reduces biot-rIgG fluxes. RT-PCR demonstrates expression of - and -subunits of rat FcRn. Northern analysis further confirms the presence of -subunit of rat FcRn mRNA of 1.6 kb. Dexamethasone exposure for 72 h decreases the steady-state level of mRNA for rat FcRn -subunit and the ab (but not ba) flux of biot-rIgG. These data indicate that IgG transport across alveolar epithelium takes place via regulable FcRn-mediated transcytosis, which may play an important role in alveolar homeostasis in health and disease.

receptor mediated; saturable transcytosis; net IgG absorption; lung defense; pulmonary immune system

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