The International Journal of Biochemistry & Cell Biology
Cells in focusAlveolar epithelial cells: Master regulators of lung homeostasis
Introduction
The most important function of the mammalian lung is gas exchange. This is supported by the alveolar epithelium, which represents 99% of the surface area of the lung. This essential cellular structure for oxygen and carbon dioxide diffusion is also constantly exposed to insults from the environment with continuous bombardment of particles, microorganisms and toxins. The highly specialized epithelium of the alveolar space must, therefore, execute simultaneously programs of oxygen provider for the entire body and of self-protection and repair. This implicates coordinated cellular and molecular processes allowing the maintenance of alveolar stability during breathing, through a dynamic interface 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.
Section snippets
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 numbers (Mason, 2006). AECIs, which are membranous flat cells usually found overlying the capillaries, provide the thin surface of the alveolus. The AECIIs are large cuboidal cells located in the alveolar corners; they display a characteristic
Gas exchange
The most remarkable feature of the alveolar region is its considerable surface of contact between air and blood required for the huge gas exchange function adapted to the human body oxygen demand (10–12,000 L of air are exchanged daily from the outside environment). During inspiration, this surface comprises approximately 150 m2 and this is made possible by the miniaturization of the lung into the very small bubble-like alveolar components (almost 500 millions in the mature lung). The local
Associated pathologies
Considering the master role of the alveolar epithelium in lung homeostasis, associated pathologies cover a very large spectrum of diseases from acute lung injury with altered clearance of pulmonary oedema fluid to chronic lung disease with fibrosis and tissue remodelling (Clement et al., 2010). Among these pathological conditions, chronic obstructive pulmonary disease (COPD) focuses much interest as it represents a major cause of death worldwide. In this context, in addition to its involvement
Future directions
Pathologies affecting the alveolar epithelium represent one of the leading causes of pulmonary morbidity and mortality, since they directly influence the whole body homeostasis through gas exchange impairment. In many situations, current medical treatments are poorly effective and ongoing research programs include the so-called regenerative medicine to rapidly restore a functional lung parenchymal surface. Among the novel orientations are cell-based therapies. These therapeutical strategies are
Acknowledgments
This work was supported by fundings from Université Pierre et Marie Curie-Paris 6, Inserm, Assistance Publique-Hôpitaux de Paris, Assistance Publique Hopitaux de Paris, Ministère de la Santé and Centre de Référence des Maladies Respiratoires Rares, Chancellerie des Universités Legs Poix, France.
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