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Nucleotide-Mediated Airway Clearance

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Purinergic Regulation of Respiratory Diseases

Part of the book series: Subcellular Biochemistry ((SCBI,volume 55))

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 P2Y2 (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 A2B (ADO) receptor-mediated responses. This chapter offers a comprehensive description of MCC and the extensive ramifications of the purinergic signaling network on pulmonary surfaces.

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Acknowledgements

The authors thank their many colleagues in their respective laboratories whose talents contributed to much of the work described in this review. We also think Edwin Chapman, University of Wisconsin, for permission to redraw Fig. 5.4 and for valuable thoughts on the mechanism of Ca2+/Syt-mediated exocytic fusion. The studies were supported in part by Grant 0120579 to PV from the Biocomplexity Program of the National Science Foundation, Grant HL-063756 to CWD from the National Institutes of Health, and grants to CWD from the North American Cystic Fibrosis Foundation.

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care, University of Miami, Miami, FL, 33136, USA

    Andreas Schmid & Mathias Salathe

  2. Department of Pharmacology, School of Medicine, St George’s University, Grenada, West Indies

    Lucy A. Clunes

  3. Department of Bioengineering, University of Washington, Friday Harbor, WA, 98195, USA

    Pedro Verdugo

  4. Institute of General Physiology, University of Ulm, Ulm, 89081, Germany

    Paul Dietl

  5. Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina, 7011 Thurston-Bowles building, Chapel Hill, NC, 27599, USA

    C. William Davis & Robert Tarran

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  1. and Treatment Center, Cystic Fibrosis Pulmonary Research and T, University of North Carolina, Chapel Hill,, 27599, North Carolina, USA

    Maryse Picher

  2. University of North Carolina, - Cystic Fibrosis Pulmonary Research and, Thurston-Bowles building - 7011, CHAPEL HILL, 27599, North Carolina, USA

    Richard C. Boucher

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Schmid, A. et al. (2011). Nucleotide-Mediated Airway Clearance. In: Picher, M., Boucher, R. (eds) Purinergic Regulation of Respiratory Diseases. Subcellular Biochemistry, vol 55. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1217-1_5

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