Net absorption of IgG via FcRn-mediated transcytosis across rat alveolar epithelial cell monolayers.
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 degrees 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 degrees 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 degrees 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 alpha- and beta-subunits of rat FcRn. Northern analysis further confirms the presence of alpha-subunit of rat FcRn mRNA of approximately 1.6 kb. Dexamethasone exposure for 72 h decreases the steady-state level of mRNA for rat FcRn alpha-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.
Kim
Kwang-Jin
KJ
Dept. of Medicine, USC Keck School of Medicine, 2011 Zonal Ave., Los Angeles, CA 90033, USA. kjkim@usc.edu
Fandy
Tamer E
TE
Lee
Vincent H L
VH
Ann
David K
DK
Borok
Zea
Z
Crandall
Edward D
ED
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D005938:Glucocorticoids; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D003907:Dexamethasone; C100688:Fc receptor, neonatal