Submitted on June 4, 2007
Accepted on June 12, 2007
INTERRELATIONS/CROSSTALK BETWEEN TRANSCELLULAR TRANSPORT FUNCTION AND PARACELLULAR TIGHT JUNCTIONAL PROPERTIES IN LUNG EPITHELIAL AND ENDOTHELIAL BARRIERS
Willy Van Driessche1, James L Kreindler2, Asrar B. Malik3, Susan Margulies4, Simon A. Lewis5, and Kwang-Jin Kim6*
1 Laboratory of Physiology, Campus Gasthuisberg O&N, K.U. Leuven, Leuven, Belgium
2 Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
3 Department of Pharmacology, University of Illinois, College of Medicine, Chicago, Illinois, United States
4 Department of Bioengineering, University of Pennsylvania, United States
5 Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston,, Texas, United States
6 Medicine, University of Southern California, Will Rogers Institute Pulmonary Research Center, Los Angeles, California, United States
* To whom correspondence should be addressed. E-mail: kjkim{at}usc.edu.
In this synopsis of a symposium at EB 2007, we start with an overview of noise and impedance analyses that have been applied to various epithelial barriers. Noise analysis yields specific information about ion channels and their regulation in epithelial and endothelial barriers. Impedance analysis can yield information about apical and basolateral membrane conductances and paracellular conductance of both epithelial and endothelial barriers. Using a morphologically-based model, impedance analysis has been used to assess changes in apical and basolateral membrane surface areas and dimensions of the lateral intercellular space. Impedance analysis of an in vitro airway epithelial barrier under normal, nucleotide-stimulated and cigarette smoke exposed conditions yielded information on how activation and inhibition of secretion occur in airway epithelial cells. Similarly, impedance analysis of primary rat alveolar epithelial cell monolayer model under control and EGTA exposure conditions indicate that EGTA causes decreases in resistances of tight junctional routes as well as apical and basolateral cell membranes without causing much changes in cell capacitances. In a stretch-caused injury model of alveolar epithelium, transcellular ion transport function and paracellular permeability of solute transport appear to be differentially regulated. Finally, inhibition of caveolae-mediated transcytosis in lung endothelium led to disruption of paracellular routes, increasing the physical dimension and permeability of tight junctional region. These data together demonstrate the crosstalk between transcellular and paracellular transport (function and routes) of lung epithelial and endothelial barriers. Mechanistic (e.g., signaling cascades) information on such crosstalk remain to be determined.
