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

• Published in: American journal of physiology. Lung cellular and molecular physiology 2004-09, Vol.287 (3), p.L616-L622
• Main Authors: Kim, Kwang-Jin, Fandy, Tamer E, Lee, Vincent H. L, Ann, David K, Borok, Zea, Crandall, Edward D
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport - drug effects; Biological Transport - immunology; Cells, Cultured; Dexamethasone - pharmacology; Gene Expression - drug effects; Gene Expression - immunology; Glucocorticoids - pharmacology; Histocompatibility Antigens Class I; Immunoglobulin G - metabolism; Immunoglobulin G - pharmacology; Male; Pulmonary Alveoli - cytology; Pulmonary Alveoli - immunology; Pulmonary Alveoli - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Fc - genetics; Receptors, Fc - metabolism; Respiratory Mucosa - cytology; Respiratory Mucosa - immunology; Respiratory Mucosa - metabolism
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00121.2004

Departments of 1 Medicine, 2 Physiology and Biophysics, 3 Molecular Pharmacology and Toxicology, 5 Biomedical Engineering, 6 Pharmaceutical Sciences, 7 Ophthalmology, 8 Biochemistry and Molecular Biology, and 9 Pathology, and 4 Will 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 Address for reprint requests and other correspondence: K.-J. Kim, Rm. HMR 914, Dept. of Medicine, USC Keck School of Medicine, 2011 Zonal Ave., Los Angeles, CA 90033 (E-mail: kjkim{at}usc.edu )