• Duncan F Rogers.
• Airway Disease, National Heart & Lung Institute, Imperial College London, Dovehouse Street, London, United Kingdom, SW3 6LY. duncan.rogers@imperial.ac.uk
• Resp Care. 2007 Sep 1; 52 (9): 1134-46; discussion 1146-9.

AbstractMucus secretion is the first-line defense against the barrage of irritants that inhalation of approximately 500 L of air an hour brings into the lungs. The inhaled soot, dust, microbes, and gases can all damage the airway epithelium. Consequently, mucus secretion is extremely rapid, occurring in tens of milliseconds. In addition, mucus is held in cytoplasmic granules in a highly condensed state in which high concentrations of Ca(2+) nullify the repulsive forces of the highly polyanionic mucin molecules. Upon initiation of secretion and dilution of the Ca(2+), the repulsion forces of the mucin molecules cause many-hundred-fold swelling of the secreted mucus, to cover and protect the epithelium. Secretion is a highly regulated process, with coordination by several molecules, including soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) proteins, myristoylated alanine-rich C kinase substrate (MARCKS), and Munc proteins, to dock the mucin granules to the secretory cell membrane prior to exocytosis. Because mucus secretion appears to be such a fundamental airway homeostatic process, virtually all regulatory and inflammatory mediators and interventions that have been investigated increase secretion acutely. When given longer-term, many of these same mediators also increase mucin gene expression and mucin synthesis, and induce goblet cell hyperplasia. These responses induce (in contrast to the protective effects of acute secretion) long-term, chronic hypersecretion of airway mucus, which contributes to respiratory disease. In this case the homeostatic, protective function of airway mucus secretion is lost, and, instead, mucus hypersecretion contributes to pathophysiology of a number of severe respiratory conditions, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis.

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