Barrier function of airway tract epithelium

Ganesan, Shyamala; Comstock, Adam T; Sajjan, Uma S

The mammalian conducting airway can be broadly divided into two regions based on structure and function: the cartilaginous proximal airway starting from nasal cavities to bronchi and 2-3 generations of bronchioles, and non-cartilaginous distal airway consisting of terminal and respiratory bronchioles. Luminal surfaces of the entire conductive airway tract are lined by a continuous layer of epithelial cells which vary in relative distribution, abundance, and cell type depending on the airway region in which they are found. The proximal airway through the bronchi is lined with pseudostratified epithelium and is made up of three major cell types: ciliated cells, non-ciliated secretory cells, and basal cells (Fig. 1) . As the bronchi branches into bronchioles and to terminal bronchioles the epithelium gradually changes from psuedostratified to simple cuboidal epithelium and the number of ciliated, goblet, and basal cells gradually decline and non-ciliated cells called Clara cells becomes the major cell type. 2 In the proximal airway and cartilaginous bronchioles, the invagination of epithelium forms submucosal glands, which are characterized by a variable proportion of ciliated cells, goblet cells, and serous cells. 3 Other minor cell types that are present in conducting airways are: (1) chemosensory or brush cells which contains apical tufts of microvilli and are thought to play a role in regulation of both airway surface fluid secretion and breathing, 4, 5 and (2) pulmonary neuroendocrine cells which are typically tall and pyramidal in shape and extend from the basal lamina of the epithelium and possess microvilli. 6, 7 Ciliated cells account for over 50% of all epithelial cells in the conducting airway. 8 Approximately 200 to 300 cilia are found on the luminal surface of each ciliated cell, and in humans the length of the cilia ranges between 6 μM in the proximal airways to 3.6 μM in the seventh generation of bronchi. 9 A large number of mitochondria are present right below the apical surface and provide energy to the cilia for coordinated ciliary beating. 10 Ciliated cells are believed to be terminally differentiated and arise from basal or secretory cells. 11, 12 However, recent studies have suggested a remarkable plasticity and differentiation potential for ciliated cells. After injury, ciliated cells dedifferentiate into squamous, cuboidal or columnar cells, thereby playing a role in restoration and regeneration of bronchial epithelium. 13