Cystic Fibrosis Research Today is a free monthly online journal that collates and summarizes the latest research about Cystic Fibrosis, including details on symptoms, genetics, treatment, information.

Reevaluating gel-forming mucins' roles in cystic fibrosis lung disease.

Perez-Vilar J, Boucher RC

The Cystic Fibrosis/Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina at Chapel Hill, CB7248, 4011 Thurston-Bowles Bldg., Chapel Hill, NC 27599, USA. juan_vilar@med.unc.edu

The existence of mucus plugs, containing mucins, bacteria, and neutrophils, blocking the lower airways in the lung of cystic fibrosis (CF) patients has raised the possibility that production of "abnormal" mucins is a critical characteristic of this disease. The molecular nature, if any, of this abnormality is unknown. Recent studies suggest that CF lung disease progression is characterized by an early phase in which airway surface liquid (ASL) increased dehydration is accompanied by altered pH and levels of reduced glutathione (GSH). In a later phase, bacterial infection and neutrophil invasion lead to increased ASL of concentrations myeloperoxidase and hypochlorous acid (HOCl). Independent studies indicate that gel-forming mucins, the key components of airway mucus, form disulfide-linked polymers through a pH-dependent, likely self-catalyzed mechanism. In this article, we present the hypothesis that increased mucus concentration (dehydration) and altered pH, and levels of GSH, myeloperoxidase, and/or HOCl result in the extracellular formation of additional interchain bonds among airway mucins. These novel interactions would create an atypical mucin network with abnormal viscoelastic and adhesive properties.

Published 12 October 2004 in Free Radic Biol Med, 37(10): 1564-77.
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