Please cite this article in press as: Guillot L, et al. Alveolar epithelial cells: Master regulators of lung homeostasis. Int J Biochem Cell Biol (2013), http://dx.doi.org/10.1016/j.biocel.2013.08.009 ARTICLE IN PRESS G Model BC 4124 1–6 The International Journal of Biochemistry & Cell Biology xxx (2013) xxx–xxx Contents lists available at ScienceDirect The International Journal of Biochemistry & Cell Biology journal h om epage: www.elsevier.com/locate/biocel Cells in focus Alveolar epithelial cells: Master regulators of lung homeostasis Loïc Guillot a,b , Nadia Nathan a,b,c , Olivier Tabary a,b , Guillaume Thouvenin a,b,c , Q1 Philippe Le Rouzic a,b , Harriet Corvol a,b,c , Serge Amselem b,d , Annick Clement a,b,c,∗ a Inserm, UMR S-938, F-75012 Paris, France b UPMC Univ Paris 06, F-75005 Paris, France c AP-HP, Hôpital Trousseau, Department of Paediatric Pulmonary Diseases, F-75012 Paris, France d Inserm, UMR S-933, F-75012 Paris, France a r t i c l e i n f o Article history: Received 24 May 2013 Received in revised form 12 July 2013 Accepted 16 August 2013 Available online xxx Keywords: Lung Alveoli Epithelium a b s t r a c t The lung interfaces with the environment across a continuous epithelium composed of various cell types along the proximal and distal airways. At the alveolar structure level, the epithelium, which is composed of type I and type II alveolar epithelial cells, represents a critical component of lung homeostasis. Indeed, its fundamental role is to provide an extensive surface for gas exchange. Additional functions that act to preserve the capacity for such unique gas transfer have been progressively identified. The alveolar epithelium represents a physical barrier that protects from environmental insults by segregating inhaled foreign agents and regulating water and ions transport, thereby contributing to the maintenance of alve- olar surface fluid balance. The homeostatic role of alveolar epithelium relies on the regulated/controlled production of the pulmonary surfactant, which is not only a key determinant of alveolar mechanical stability but also a complex structure that participates in the cross-talk between local cells and the lung immune and inflammatory response. In regard to these critical functions, a major point is the mainte- nance of alveolar surface integrity, which relies on the renewal capacity of type II alveolar epithelial cells, and the contribution of progenitor populations within the lung. © 2013 Elsevier Ltd. All rights reserved. Cell facts • The alveolar epithelium, composed of type I and type II alve- olar epithelial cells, represents 99% of the surface area of the lung. • Alveolar epithelial cells are important contributors of lung development and repair through their plasticity and self- renewal capacity. • Alveolar epithelial cell morphology and dynamic ensure a close contact between air and blood for an efficient diffusion of the breathing gases. • Alveolar epithelial cells have important defence and immunomodulatory functions. 1. Introduction The most important function of the mammalian lung is gas exchange. This is supported by the alveolar epithelium, which ∗ Corresponding author at: AP-HP, Hôpital Trousseau, Department of Paediatric Pulmonary Diseases, F-75012 Paris, France. Tel.: +33 1 44 73 66 68. E-mail address: annick.clement@trs.aphp.fr (A. Clement). represents 99% of the surface area of the lung. This essential cel- lular structure for oxygen and carbon dioxide diffusion is also constantly exposed to insults from the environment with contin- uous bombardment of particles, microorganisms and toxins. The highly specialized epithelium of the alveolar space must, there- fore, execute simultaneously programs of oxygen provider for the entire body and of self-protection and repair. This implicates coor- dinated cellular and molecular processes allowing the maintenance of alveolar stability during breathing, through a dynamic inter- face with the environment composed of the surfactant surface film and a small amount of alveolar fluid. This focus reviews current understanding of the plasticity and critical functions of the alveolar epithelium that are essential for lung homeostasis. 2. Cell origin and plasticity The mature alveolar epithelium consists of type I and type II alveolar epithelial cells (AECI and AECII), also called type I and type II pneumocytes, which occupy about 96% and 4% respectively of the surface, although they are present in roughly similar num- bers (Mason, 2006). AECIs, which are membranous flat cells usually found overlying the capillaries, provide the thin surface of the alve- olus. The AECIIs are large cuboidal cells located in the alveolar corners; they display a characteristic morphology with so-called lamellar bodies and apical microvilli. 1357-2725/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.biocel.2013.08.009 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46