Physiological Impact of Abnormal Lipoxin A₄ Production on Cystic Fibrosis Airway Epithelium and Therapeutic Potential

Figure 2

In normal airways the airway surface liquid layer (ASL) provides an adequate mucociliary clearance which is maintained by a combination of Cl⁻ secretion through the cystic fibrosis transmembrane conductance regulator (CFTR), Na⁺ absorption via the epithelial sodium channel (ENaC), and water transport through a paracellular pathway and membrane bound aquaporins (Aq). In CF, a defective CFTR leads to loss of Cl⁻ secretion and Na⁺ hyperabsorption. The concomitant dehydration of the airway lumen favours bacterial infection and inflammation (mainly neutrophilic). LXA₄ mediates an increase in ASL height and restores it to normal levels in CF bronchial epithelium. LXA₄ also increase tight junction formation, reestablishing the epithelial barrier function. Taken together this work provides evidence for LXA₄ as potentially a new therapy for CF patients.