Alan D. Jackson

Airway goblet-cell mucus secretion.

A mucus hypersecretory phenotype is a dominant characteristic of chronic airways diseases such as chronic bronchitis and asthma. This phenotype develops following chronic exposure of the respiratory tract to particulate matter, allergens, irritants and/or pathogens. The associated increase in the mucus-producing potential of the respiratory epithelium represents an innate host response that can be modulated by elements of the adaptive host response. Although elevation of mucus production is designed to protect the airways, increasing evidence suggests that in excess it can be detrimental to health. Considerable progress has been made over the past five years in understanding the mechanisms involved in the development and regulation of the hypersecretory phenotype. This progress has set the stage for the development of successful dedicated mucomodulatory strategies to counter the negative impact of excess mucus production in respiratory disease.

Epithelial mucus-hypersecretion and respiratory disease.

Mucus production, secretion and clearance are considered to play a critical role in maintenance of airway health, however in diseases such as COPD, epidemiological and pathological studies suggest that excess mucus contributes to airway plugging and decline in lung health. The airway surface epithelium is composed of a heterogeneous mix of cell types one of which, the goblet cell, is dedicated to the production of secretory gel-forming mucins. Changes in epithelial cellular composition and function in response to irritants and microbes generally leads to enhanced co-ordinated functioning of the major facets of the mucociliary clearance (MCC) system i.e. mucus secretion, ion/fluid transport and ciliary function. The presence of mucus plugs in the airways of COPD patients demonstrates that facets of the MCC system have become compromised i.e. normally co-ordinated epithelial functions have become uncoupled. Almost nothing is known about the processes leading to such uncoupling. Understanding these processes may provide insights into mechanisms involved in regulation of epithelial integrity and the genesis of respiratory diseases such as COPD. In this review we will discuss regulation of airway epithelial cellular composition and function primarily with respect to goblet cell formation, mucus secretion, airway surface liquid (ASL) homeostasis, hydration of secreted mucus and ciliary clearance. We will discuss the functional overlap between cell populations, the potential impact of derivation from different progenitors and the implications of generating high goblet cell densities in the surface epithelium. The aim of this review is to stimulate discussion and develop hypotheses that could help to determine the mechanisms behind epithelial dysfunction in respiratory disease.