Nucleotide-Mediated Airway Clearance

Abstract

A thin layer of airway surface liquid (ASL) lines the entire surface of the lung and is the first point of contact between the lung and the environment. Surfactants contained within this layer are secreted in the alveolar region and are required to maintain a low surface tension and to prevent alveolar collapse. Mucins are secreted into the ASL throughout the respiratory tract and serve to intercept inhaled pathogens, allergens and toxins. Their removal by mucociliary clearance (MCC) is facilitated by cilia beating and hydration of the ASL by active ion transport. Throughout the lung, secretion, ion transport and cilia beating are under purinergic control. Pulmonary epithelia release ATP into the ASL which acts in an autocrine fashion on P2Y(2) (ATP) receptors. The enzymatic network describes in Chap. 2 then mounts a secondary wave of signaling by surface conversion of ATP into adenosine (ADO), which induces A(2B) (ADO) receptor-mediated responses. This chapter offers a comprehensive description of MCC and the extensive ramifications of the purinergic signaling network on pulmonary surfaces.

Tobacco Smoke Constituents Trigger Cytoplasmic Calcium Release

“…16,17 In the airways, Ca 2+ also regulates ciliary beating, 18,19 Cl À /ASL secretion, 20 cytokine secretion, and mucin secretion. 21 The majority of cytoplasmic Ca 2+ emanates from the endoplasmic reticulum and excess cytoplasmic Ca 2+ are usually rapidly taken up into this store soon after release. This is desirable because Ca 2+ is usually only transiently elevated as a cytoplasmic second messenger.…”

Cigarette Smoke-induced Ca2+ Release Leads to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Dysfunction

“…Innate lung defense includes mucus clearance, a process that continuously cleans the respiratory tract (3). To maintain mucus clearance, salt and water must be secreted into the lung to balance secretion of "dry" mucins, and together, this mucus/airway surface liquid (ASL) 2 is cleared either by ciliary beat or by coughing (3).…”

“…Innate lung defense includes mucus clearance, a process that continuously cleans the respiratory tract (3). To maintain mucus clearance, salt and water must be secreted into the lung to balance secretion of "dry" mucins, and together, this mucus/airway surface liquid (ASL) 2 is cleared either by ciliary beat or by coughing (3). When lung inflammation is triggered, normally both salt/water and mucin secretion are enhanced, which serves to increase rates of mucus clearance, thus washing the lung more frequently, until the cause of the infection is resolved (3).…”

Dual Oxidase 2 (Duox2) Regulates Pannexin 1-mediated ATP Release in Primary Human Airway Epithelial Cells via Changes in Intracellular pH and Not H2O2 Production

“…ATP is a key regulator of the innate pulmonary host defense by activating purinergic P2Y2 receptors, which promote chloride secretion by calcium-activated Cl Ϫ channels, inhibit Na ϩ absorption by epithelial Na ϩ channels, increase ciliary beat frequency and airway surface liquid volume, and induce mucin release, thereby activating mucociliary clearance (1)(2)(3)(4). Although the effects of ATP on airway epithelial cells have been studied widely, Panx1 channels have only been recognized recently to be involved in ATP release in these tissues (5,6).…”