Computational Model for the Regulation of Extracellular ATP and Adenosine in Airway Epithelia

摘要: Extracellular nucleotides are key components of the signaling network regulating airway clearance. They released by epithelium into surface liquid (ASL) to stimulate cilia beating activity, mucus secretion and hydration. Understanding factors affecting their availability for purinoceptor activation is an important step toward development new therapies obstructive lung diseases. This chapter presents a mathematical model developed gain predictive insights regulation ASL nucleotide concentrations on human epithelia. The parameters were estimated from experimental data collected polarized primary cultures nasal bronchial epithelial cells. reproduces major observations: (1) independence steady-state height, (2) impact selective ectonucleotidase inhibitors concentrations, (3) changes in composition caused mechanical stress mimicking normal breathing, (4) differences existing between In addition, this launched study release uncharted territories, which led discovery that epithelia release, not only ATP, but also ADP AMP. shows computational modeling, coupled validation, provides powerful approach identification therapeutic targets improvement clearance respiratory