Respiratory diseases are a predominant cause of illness in pediatric populations and a major cause of mortality among children in undeveloped countries. Our laboratory has worked for over fifteen years in the cell biology, developmental biology, and pathology of the mammalian conducting airways and lung. Much of our focus has been on the ciliated cells of the airways which comprise an integral element of mucociliary clearance. The ciliated cells working in a coordinated fashion with mucus secreting cells represent a primary line of defense to the respiratory tract and our work has documented that structural integrity of the cilia is critically linked to optimal mucociliary function. Our studies also have shown that while the ciliated cell is functionally critical to optimal mucociliary clearance, it also is one of the most vulnerable to injury by microbiologic infectious agents and ambient air pollutants. These studies led to the characterization of acquired ciliary defects in the respiratory epithelium in contrast to primary ciliary defects which derive from genetically heritable conditions and also impose ciliary dysfunction and subsequent chronic respiratory disease.

In addition to studies relating to ciliated cell injury, we also have ongoing projects relating to the development of the airway epithelium, particularly in the differentiation of ciliated cells. We have used as an model for these studies the infant ferret which at birth exhibits less than 10% ciliated cells lining the conducting airways. However, the airways undergo rapid maturation with accompanying ciliated cell differentiation over the first month of life. Additionally, the ferret is particularly susceptible to infection by influenza virus, a factor which facilitates studies of infectious disease pathogenesis of the airways. We have conducted a number of investigations on ferret airways including studies of the attachment of influenza virus to ciliated and ciliating cells, patterns of ciliogenesis in the airways, and the role of gap junctions in early airway development.

Carson, J. L., Collier, A. M., Hu, S. S., McLachlan, J. B. 1995. Variability in the distribution and populations of gap junctions in the ferret trachea during post-natal development. In Press: Am. J. Physiol.: Lung Cell & Molec. Physiol. 15pp.

Carson, J. L., Collier, A. M., Fernald, G. W., Hu, S. S. 1994. Microtubular discontinuities as acquired ciliary defects in airway epithelium of patients with chronic respiratory disease. Ultrastruct. Pathol. 18:327-332.

Carson, J. L., A. M. Collier, S. S. Hu, R. B. Devlin. 1993. The effect of nitrogen dioxide on human nasal epithelium. Am. J. Resp. Cell Mol. Biol 9:264-270.

Carson, J. L., Collier, A. M., Gambling, T. M., Knowles, M. R., Boucher, R. C. 1990. Ultrastructure of airway epithelial cell membranes among patients with cystic fibrosis. Human Pathology 21:640-647.

Carson, J. L., Willumsen, N. J., Gambling, T. M., Hu, S. S., Collier, A. M. 1989. Dynamics of intercellular communication and differentiation in a rapidly developing mammalian airway epithelium. Am. J. Respir. Cell & Molec. Biol. 1:385-390.