Role of mechanical stress in regulating airway surface hydration and mucus clearance rates.
Effective clearance of mucus is a critical innate airway defense mechanism, and under appropriate conditions, can be stimulated to enhance clearance of inhaled pathogens. It has become increasingly clear that extracellular nucleotides (ATP and UTP) and nucleosides (adenosine) are important regulators of mucus clearance in the airways as a result of their ability to stimulate fluid secretion, mucus hydration, and cilia beat frequency (CBF). One ubiquitous mechanism to stimulate ATP release is through external mechanical stress. This article addresses the role of physiologically relevant mechanical forces in the lung and their effects on regulating mucociliary clearance (MCC). The effects of mechanical forces on the stimulating ATP release, fluid secretion, CBF, and MCC are discussed. Also discussed is evidence suggesting that airway hydration and stimulation of MCC by stress-mediated ATP release may play a role in several therapeutic strategies directed at improving mucus clearance in patients with obstructive lung diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
Button
Brian
B
Cystic Fibrosis Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248, USA. bbutton@med.unc.edu
Boucher
Richard C
RC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D009079:Mucociliary Clearance / Q000502:physiology*; D020545:Respiratory Mucosa / Q000502:physiology*; D012140:Respiratory Tract Diseases / Q000378:metabolism / Q000503:physiopathology; D013314:Stress, Mechanical
D000255:Adenosine Triphosphate