Regulation of the depth and composition of airway surface liquid

Abstract

The airways are lined with a film of liquid about 10 microm deep that is in two layers. Around the cilia is the watery periciliary sol. Over this is a mucous blanket that traps inhaled particles. The low viscosity of the periciliary sol allows the cilia to beat and propel the mucous blanket to the mouth. In large airways, mucus comes predominantly from the mucous glands but also from goblet cells in the surface epithelium. Water is added to the airway surface by gland secretion that is driven by active Cl secretion by serous cells. During inflammation elevation of the subepithelial hydrostatic pressure may also add significant volumes of water to the airway lumen. Water is removed by active Na transport across the surface epithelium. In airway diseases, the balance is shifted from water secretion to mucus secretion. In bronchitis and asthma this is due mainly to conversion of gland serous to mucous cells. In cystic fibrosis, gland serous cells cannot secrete water because they lack functioning CFTR in their apical membranes (CFTR is the cystic fibrosis transmembrane conductance regulator, a Cl channel that is abundant in serous cells). In all three diseases, the result is secretion of excessively concentrated gland secretions that are poorly moved by the cilia and accumulate. Altered salt and water transport by the surface epithelium may also contribute to the pathology of cystic fibrosis.

Fig. 1

The two-layer hypothesis for airway secretions. (a) As originally proposed by Lucas & Douglas (1934). (b) Two layers in rapidly frozen cultures of rabbit tracheal epithelium (Sanderson & Sleigh, 1981). (c) Two layers as revealed by electron microscopy of rat trachea (Yoneda, 1976).

Fig. 2

Submucosal glands. (a) Openings on surface of bovine trachea as seen by scanning electron microscopy. Note variability in size and frequency of ˜1.5 per mm². Scale bar = 1 mm (from Iovannitti et al. 1985). (b) Submucosal glands in pig trachea visualized by PAS/Alcian blue staining. One complete gland is shown and parts of two others. Arrowheads show gland openings. Mucus is issuing from the opening indicated by the white arrowhead. Scale bar = 200 μm.

Fig. 3

Effects of methacholine on depth of airway surface liquid. (a) Control tissue not exposed to methacholine; C, cilia. (b) 2-min methacholine exposure. Putative sol (S) and gel (G) have been identified based on difference in size of ice crystal voids created by radiant etching. Note that, unusually, the sol appears deeper than the length of the cilia. (c) 30-min exposure. Scale bar = 20 mm. *Goblet cells. From Wu et al. (1998)