Mucus Secretion and Calcium Mobilization in Airway Submucosal Gland Cell

Airway mucus secretion from submucosal gland cells (SMGC) plays an important role in protecting the respiratory system from pathogens and particles. However, mucus hypersecretion is a common pathophysiological characteristic of many chronic inflammatory pulmonary diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, and asthma that can lead to airway obstruction and impaired gas exchange, and if serious enough even plug the airways, possibly leading to death. Both hyperplasias of submucusosal glands and increased sensitivity of SMGC to various secretagogues such as neurotransmitters and hormones play roles in mucus hypersecretion. Acute increases in mucus release are the result of sensitization of SMGC. Therefore, understanding the mechanisms of mucus secretion and its sensitization will provide potential targets for therapies that would be beneficial in the treatment of chronic inflammatory lung diseases. The submucosal gland is comprised of serous cell and mucous cell ascini. Serous cells secrete water, electrolytes and some mucin, while mucous cells secrete mainly mucin but also some fluid. Mucin, a highly glycosylated protein, is the main macromolecular component of airway-secreted mucus. It forms high molecular weight chains that are packaged within SMGC in vesicles that are released by exocytosis upon activation of the SMGC by a stimulus. An increase in intracellular Ca is required for ion movement and evoked mucin release stimulated by secretagogues such as acetylcholine (Ach), histamine, or ATP. In SMGC, membrane receptor activation induces Ca release from internal stores and subsequent Ca influx through store-operated Ca channels (SOC) or receptor-operated channels (ROC).