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

Figure 3

Lipoxin A₄ enhances epithelial barrier integrity by stimulating an increase in airway surface liquid (ASL) layer height, epithelial repair, and tight junction formation. Stimulation of the FPR2 receptor by LXA₄ induces an apical ATP release through the pannexin (Panx1) channel activating a purinoreceptor pathway. Activation of P2Y11 receptors stimulates chloride secretion out of the cell by calcium activated chloride channels (CaCC) and inhibition of sodium absorption by amiloride sensitive epithelial sodium channels (ENaC) which result in a restored ASL height in CF bronchial epithelial cells. The calcium signal induced by P2Y11 activation also stimulates epithelial repair and tight junction formation. Taken together, the physiological effects induced by LXA₄ have the potential to delay the invasion of bronchial epithelial cells by bacteria (green and orange structures).