Regulation of depth and composition of airway surface liquid

Abstract

R Re eg gu ul la at ti io on n o of f d de ep pt th h a an nd d c co om mp po os si it ti io on n o of f a ai ir rw wa ay y s su ur rf fa ac ce e l li iq qu ui id dThe airways are lined with a film of fluid, which is 5-20 µm deep in healthy individuals. This fluid is believed to consist of two phases [1]. A watery fluid of low viscosity, the "periciliary sol" surrounds the cilia. Above this lies a viscous mucous gel. The cilia are able to beat in the sol. Their tips contact the underside of the mucous blanket and propel it towards the mouth. This system of "mucociliary clearance" serves to remove particles trapped in the mucous gel. The concept of two layers of airway surface liquid (ASL) has been supported by a variety of microscopy studies [2][3][4][5] (fig. 1).Factors influencing the liquid content of sol and gel have been identified but their relative contributions are imperfectly understood. Water will move into the airway lumen in response to active Cl -secretion across the epithelia of the tracheal surface and of submucosal glands. Active absorption of Na + across the surface epithelium serves to remove liquid. These active ion transport processes move liquid by generating local osmotic gradients across the epithelium [6]. Hydrostatic pressure gradients across the epithelium, and differences in osmotic pressure between the media bathing the epithelium's two surfaces, will also influence the net movement of liquid into or out of the lumen. Evaporation is an important factor in the upper airways. Finally, forces of surface tension generated by the closely packed cilia SERIES "AIRWAY MUCUS" Edited by P.K. JefferyNumber 6 in this Series may serve to hold liquid in the airway lumen [7]. These factors are considered in turn below. Additionally, we describe recent experiments in which we have used lowtemperature scanning electron microscope (LT-SEM) to determine the depth and composition of the airway surface liquid (ASL). Gland secretionThe adult human trachea has about 10 submucosal gland openings per mm 2 of airway surface [8]. It is unknown how the structure and numbers of glands change down the airways, except that bronchi have glands, whereas bronchioles do not [9]. In each gland, a ciliated duct leads from the airway surface to an expanded collecting duct into which empty ~10 secretory tubules, each with multiple branches ending in closed acini [10]. The acini are lined by serous cells, the tubules by mucous cells [11]. It is believed that the serous cells secrete fluid which serves to flush out mucins released by the more proximal mucous cells [12]. Consistent with this hypothesis, gland serous cells contain much the highest levels of the cystic fibrosis transmembrane conductance regulator of any cell type in the airways [13] Respir J 1997; 10: 1914-1917

Complex Fluids and Soft Structures in the Human Body

“…The PCL in healthy conditions is ∼ 7 μm thick [92,93]. The thickness of the luminal mucus layer varies throughout the respiratory tract, increasing from distal to proximal airways [93,94].…”

Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses

“…Existence of non-motile cilia is discussed in cells without central double tubules acting as sensory antenna. Cilia are covered by a 10–15 µm thick layer of mucus, filling also the spaces between cilia [8]. In respiratory mucosa, goblet cells and seromucous glands in the adjacent connective tissue are typically found.…”

Biomarkers of lung‐related diseases: Current knowledge by proteomic approaches

“…It is suggested that T-helper type 2 lymphocytes, and the cytokines that they produce, in conjunction with reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by inflammatory and epithelial cells, contributed as the key mediators of the chronic airway inflammation of asthma (Calhoun et al, 1992;Horwitz and Busse, 1995;Renauld, 2001;Zhou et al, 2001). The airway surface is covered by a thin fluid layer, termed as the airway surface liquid and this acts as a barrier to protect the underlying epithelium (Widdicombe, 2002). The identification of secreted proteins in this fluid may be important in understanding the etiology of asthma.…”