Cells in focusThe airway goblet cell
Introduction
Goblet cells are found in the surface epithelium of the upper and lower respiratory tract, a location that befits first line defence of the airways (Fig. 1, panels A and B). They rapidly secrete high molecular weight mucous glycoproteins (termed mucins) to protect the epithelial lining from the battery of dusts, fumes, microorganisms and other debris delivered by inhalation of ∼12,000 l of air per day. The mucins mix with other protein, lipid and glycoconjugate components in a dilute aqueous solution often referred to as ‘mucus’. Mucus interacts with the tips of beating cilia and is wafted towards the mouth and swallowed. Particles trapped in the mucus are thereby removed from the airways, a process termed mucociliary clearance. As an adjunct to mucociliary clearance, excessive amounts of mucus, produced as part of a pathophysiological condition such as asthma or chronic obstructive pulmonary disease (COPD), can be dislodged by cough and then expectorated. The viscosity and elasticity of the mucus determine its efficiency of coupling to cilia. It is the mucins, albeit comprising <2% of the wet weight of the mucus, which confer the requisite viscoelasticity for effective mucociliary transport. Mucins are also secreted by submucosal glands (Fig. 1, panel A). However, submucosal glands are found only in cartilaginous airways. In contrast, goblet cells are found throughout the conducting airways and consequently are the sole source of mucins in the non-cartilaginous bronchioles. In respiratory diseases with mucus hypersecretion as a clinical feature, including asthma and COPD, goblet cells become increased in number (Fig. 2) [1]. There may also be changes in the size and shape of the goblet cells, for example a narrowing and elongation in response to epithelial proliferation, which may account for the widely disparate dimensions of goblet cells seen in micrographs of human airways (Fig. 1, panel B). In the large airways where goblet cells are normally present, the increase in number in hypersecretory conditions is referred to as a hyperplasia. In the smallest conducting airways (<2 mm in diameter) where goblet cells are normally scarce or absent, the appearance and subsequent hyperplasia of goblet cells is referred to as metaplasia. Goblet cell metaplasia in small airways with subsequent hypersecretion can readily compromise mucociliary transport, leading to mucus trapping and airflow obstruction. Thus, the acute protective role of goblet cell mucin secretion becomes pathophysiological and contributes to respiratory disease.
The present short article summarises the more recent advances in understanding of the mechanisms underlying the above dual activities of airway goblet cells, namely mucin secretion and the ability to change in number.
Section snippets
Primary function: mucin secretion
The primary function of goblet cells is to secrete mucins onto the internal surface of the airways. A variety of inflammatory mediators, irritant gases and other experimental interventions (e.g. oxidant stress) induce goblet cell secretion in vivo in experimental animals and in vitro in explant cultures, although fewer of these stimuli induce secretion in cultured respiratory epithelial secretory cells [2], [3]. The nature of goblet cell mucins and the mechanisms underlying their secretion are
Origin and plasticity of airway goblet cells
Goblet cells increase dramatically in number, in response to a variety of airway ‘insults’, including cigarette smoke, irritant gases such as sulphur dioxide, proteinases, inflammatory mediators and bacterial products (Fig. 2) [2]. The new goblet cells appear to arise by differentiation of non-granulated progenitor cells, including basal cells, rather than via goblet cell division [2], [10]. The increase in number is associated with increased MUC gene expression and increased mucin production.
Pathophysiology, clinical implications and potential therapy
Airway goblet cell hyperplasia is a pathophysiological feature of a number of severe respiratory diseases, including asthma and COPD [2]. The associated hypersecretion of mucin, leading to changes in the volume and biophysical properties of airway mucus, in particular in small airways, are associated with patient morbidity and with mortality of certain groups of patients, for example elderly COPD patients who are prone to chest infections. Consequently, suppression or reversal of goblet cell
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