Molecular insight into increased risk of lung infections in those with cystic fibrosis

https://www.the-jci.org/article.php?id=37284


Summary:

Chronic bacterial infections of the airways are one of the major causes of death in individuals with cystic fibrosis, an inherited disease caused by disruption to the function of the CFTR protein. Jeffrey Wine and colleagues, at Stanford University, California, have now provided new molecular insight into how disruption of CFTR function in the human lung impairs the secretion of fluids that are required for the action of immune defense mediators in the lung.

The fluids important for immune mediators in the lungs are released from airway glands known as submucosal glands following stimulation by nerves that release a number of factors, including substance P. In the study, fluid secretion mediated by substance P was measured from isolated human submucosal glands and intact lung transplant tissue. Irritants were unable to stimulate substance P-induced production of fluids by glands from individuals with cystic fibrosis. Further, glands from individuals with cystic fibrosis did not respond to substance P, whereas glands from healthy individuals secreted fluids. The authors therefore conclude that CFTR is required for substance P-induced production of fluids by submucosal glands and suggest that a defect in this pathway following exposure to lung irritants contributes to the susceptibility to airway infection seen in individuals with cystic fibrosis.

TITLE: Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process