Distribution of vascular connexin proteins in the airway epithelium of the rat: evidence for myo-epithelial gap junctions

Newcastle University (2009) Proc Physiol Soc 16, C21

Oral Communications: Distribution of vascular connexin proteins in the airway epithelium of the rat: evidence for myo-epithelial gap junctions

M. Zbaeda1, T. Kamishima1, J. Quayle1, K. Stuart-Smith2

1. Department of Human Anatomy and Cell Biology, University of Liverpool, Liverpool, United Kingdom. 2. Anaesthesia, Glan Clwyd Hospital, Rhyl, United Kingdom.

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Introduction Interendothelial and myoendothelial gap junctions are well described in the vascular system. However, little is known about the role of inter-epithelial gap junctions of the lung. The airway epithelium acts as a functional syncitium. Failure of this system is a crucial part of the pathology of diseases such as cystic fibrosis and acute respiratory distress syndrome. Furthermore, the function of the lung depends on the interaction between airway and blood vessels for gas exchange, and the pulmonary vessels and bronchi may have a common embryological origin1. It is hypothesised that these tissues have connexin proteins in common. This study looked at the distribution of vascular connexin proteins in the airways. Methods Slices from the first intrapulmonary bronchus and peripheral bronchioles (50-100μm diameter) of the rat were dual-labelled using connexin (Cx) 37, 40 or 43 antibody and α-actin antibody, and visualized for confocal microscopy using AF488 and AF594. Results Connexin 43 was abundantly distributed along the inter-epithelial borders of the first intrapulmonary bronchus. Connexin 37 seems absent from this large airway. Connexin 40 showed faint staining along the epithelial borders, but showed much more abundant staining along the areas of contact between the base of the epithelium and the underlying airway smooth muscle. Co-staining with α-actin demonstrated that connexin 40 in the primary bronchus was clearly associated with smooth muscle. However, connexin 40 staining was found primarily along the smooth muscle-epithelial cell border with little signal coming from deeper smooth muscle layers. In the peripheral bronchiole, connexin 37 was found along the border between the smooth muscle and epithelium, but seemed absent in either the deeper smooth muscle border or along the borders between epithelial cells. Both connexin 40 and connexin 43 were abundantly present in the epithelial tissue of the peripheral airway. Conclusion To our knowledge these data represent the first demonstration of blood vessel-related connexin proteins in the respiratory epithelium of conducting airways. Although connexin 43 expression between alveolar cells has been described 2, there are almost no studies of connexin communication in the respiratory epithelial syncitium. Our data show variation in connexin proteins along the respiratory tree, with connexin 37 being absent in large airways but abundant in peripheral bronchioles. In addition there is exciting new evidence to suggest myo-epithelial gap junctions, which could modulate bronchial smooth muscle tone. The ability of the respiratory epithelium to influence bronchial smooth muscle tone was described in the past 3, but the mechanism remains unclear. Myo-epithelial junctions may form part of this mechanism.



Where applicable, experiments conform with Society ethical requirements.

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