The airway epithelium: structural and functional properties in health and disease.
The major function of the respiratory epithelium was once thought to be that of a physical barrier. However, it constitutes the interface between the internal milieu and the external environment as well as being a primary target for inhaled respiratory drugs. It also responds to changes in the external environment by secreting a large number of molecules and mediators that signal to cells of the immune system and underlying mesenchyme. Thus, the epithelium is in a unique position to translate gene-environment interactions. Normally, the epithelium has a tremendous capacity to repair itself following injury. However, evidence is rapidly accumulating to show that the airway epithelium of asthmatics is abnormal and has increased susceptibility to injury compared to normal epithelium. Areas of detachment and fragility are a characteristic feature not observed in other inflammatory diseases such as COPD. In addition to being more susceptible to damage, normal repair processes are also compromised. Failure of appropriate growth and differentiation of airway epithelial cells will cause persistent mucosal injury. The response to traditional therapy such as glucocorticoids may also be compromised. However, whether the differences observed in asthmatic epithelium are a cause of or secondary to the development of the disease remains unanswered. Strategies to address this question include careful examination of the ontogeny of the disease in children and use of gene array technology should provide some important answers, as well as allow a better understanding of the critical role that the epithelium plays under normal conditions and in diseases such as asthma.
Knight
Darryl A
DA
Asthma and Allergy Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. dknight@cyllene.uwa.edu.au
Holgate
Stephen T
ST
D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D001485:Basement Membrane / Q000033:anatomy & histology / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D009490:Neurosecretory Systems / Q000166:cytology; D020545:Respiratory Mucosa / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*
D005938:Glucocorticoids; D006133:Growth Substances