| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA, USA; Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, CA, USA
2 Department of Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA
3 Department of Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA; Department of Ophthalmology, University of Southern California, Los Angeles, CA, USA
4 Department of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, CA, USA
5 Department of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA; Will Rogers Institute Pulmonary Research Center, Keck School of Medicine and Schools of Pharmacry and Engineering, University of Southern California, Los Angeles, CA, USA
6 Department of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Pathology, University of Southern California, Los Angeles, CA, USA; Will Rogers Institute Pulmonary Research Center, Keck School of Medicine and Schools of Pharmacry and Engineering, University of Southern California, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: kjkim{at}usc.edu.
Various serum proteins are known to be present in alveolar lining fluid, although the transport mechanisms underlying their presence remain unclear. In this study, 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. Specificity of IgG transport was explored by measuring unidirectional biot-rIgG fluxes in the presence of excess Fc, Fab, F(ab')2, or chicken Ig (IgY) in either apical or basolateral upstream fluid. 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 5-fold 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 Kt and Jmax of 7.1 nM and 1.3 fmol/cm2/hr. At 4°C, both ab and ba fluxes significantly decrease, collapsing net absorption. The presence of excess unlabeled Fc (but not Fab, F(ab')2, or IgY) in either apical or basolateral upstream fluid
significantly reduces the respective unidirectional biot-rIgG fluxes. RT-PCR analyses demonstrate the expression of 
- and 
-subunits of rat FcRn in rat alveolar epithelial cell monolayers. Northern analyses further confirm the presence of -subunit of rat FcRn mRNA with an estimated size of ~1.6-kb. Dexamethasone exposure for 72 hr decreases the steadystate
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 FcRnmediated transcytosis, which may play an important role in alveolar homeostasis in health and disease.
This article has been cited by other articles:
|
|
 |
|
  B. C. Willis, J. M. Liebler, K. Luby-Phelps, A. G. Nicholson, E. D. Crandall, R. M. du Bois, and Z. Borok Induction of Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells by Transforming Growth Factor-{beta}1: Potential Role in Idiopathic Pulmonary Fibrosis Am. J. Pathol., May 1, 2005; 166(5): 1321 - 1332. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
