| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2 Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA
3 Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA
4 Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
5 Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
6 Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
7 Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA
* To whom correspondence should be addressed. E-mail: ljain{at}emory.edu.
A fluid-free alveolar space is critical for normal gas exchange. Influenza virus alters fluid transport across respiratory epithelia producing rhinorrhea, middle ear effusions, and alveolar flooding. However, the mechanism of fluid retention remains unclear. We investigated the effects of influenza virus strain A/PR/8/34, which can attach and enter mammalian cells but is incapable of viral replication and productive infection in mammalian epithelia, on epithelial Na channels (ENaC) in alveolar type II (ATII) cells isolated from rat lungs and grown on permeable supports with an air interface and steroids to promote ENaC expression. In parallel, we determined the effects of the virus on amiloride-sensitive (i.e., ENaC-mediated) fluid clearance in rat lungs in vivo. Although influenza virus did not change the inulin permeability of ATII monolayers, it rapidly (within 1 hr) reduced the net volume transport from the lumenal to serosal surface of the monolayers. When single channel activity was recorded from cell-attached patches on the apical membranes of ATII cells, virus exposure resulted in a reduction in the open probability (Po) of apical ENaC. U-73122, a phospholipase C inhibitor, and PP2, a Src inhibitor, blocked the effect of virus on ENaC function. GF-109203X, a protein kinase C (PKC) inhibitor, also blocked the effect, suggesting a PKC-mediated mechanism. In parallel, intratracheal administration of influenza virus produced a rapid (within 1 hr) inhibition of amiloride-sensitive (i.e., ENaC-dependent) lung fluid transport. Taken together, these results show that influenza virus rapidly inhibits ENaC in the apical membranes of ATII cells via a PLC- and Src-mediated activation of PKC, but does not increase epithelial permeability with this same rapid time course. We speculate that this rapid inhibition of ENaC and formation of alveolar edema when the virus first attaches to the alveolar epithelium might facilitate subsequent influenza infection of the epithelium, and at the very least may exacerbate influenza-mediated alveolar flooding that can lead to acute respiratory failure and death in selected patients.
This article has been cited by other articles:
|
|
 |
|
  K. E. Wolk, E. R. Lazarowski, Z. P. Traylor, E. N. Z. Yu, N. A. Jewell, R. K. Durbin, J. E. Durbin, and I. C. Davis Influenza A Virus Inhibits Alveolar Fluid Clearance in BALB/c Mice Am. J. Respir. Crit. Care Med., November 1, 2008; 178(9): 969 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. F. Bao, L. Liu, J. Self, B. J. Duke, R. Ueno, and D. C. Eaton A synthetic prostone activates apical chloride channels in A6 epithelial cells Am J Physiol Gastrointest Liver Physiol, August 1, 2008; 295(2): G234 - G251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Eisenhut and J. P. Mizgerd Acute Lower Respiratory Tract Infection N. Engl. J. Med., May 29, 2008; 358(22): 2413 - 2414. [Full Text] [PDF]
|
|
|
|
 |
|
 H. G. Folkesson and M. A. Matthay Alveolar Epithelial Ion and Fluid Transport: Recent Progress Am. J. Respir. Cell Mol. Biol., July 1, 2006; 35(1): 10 - 19. [Full Text] [PDF]
|
|
|
|
 |
|
 X. Su, L. Robriquet, H. G. Folkesson, and M. A. Matthay Protective effect of endogenous beta-adrenergic tone on lung fluid balance in acute bacterial pneumonia in mice Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L769 - L776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Matthay, L. Robriquet, and X. Fang Alveolar Epithelium: Role in Lung Fluid Balance and Acute Lung Injury Proceedings of the ATS, October 1, 2005; 2(3): 206 - 213. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
