Alveolar epithelial cells: Master regulators of lung homeostasis

doi:10.1016/j.biocel.2013.08.009

The International Journal of Biochemistry & Cell Biology

Volume 45, Issue 11, November 2013, Pages 2568-2573

https://doi.org/10.1016/j.biocel.2013.08.009 Get rights and content

Abstract

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 alveolar 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 maintenance 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.

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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Cells in focusAlveolar epithelial cells: Master regulators of lung homeostasis

Abstract

Introduction

Section snippets

Cell origin and plasticity

Gas exchange

Associated pathologies

Future directions

Acknowledgments

Biochim Biophys Acta

Int J Biochem Cell Biol

Chest

Exp Mol Pathol

Lab Invest

Paediatr Respir Rev

Cell

Cell

Hum Pathol

Int J Biochem Cell Biol

Biochim Biophys Acta

Int J Biochem Cell Biol

Surfactant protein-D regulates effector cell function and fibrotic lung remodeling in response to bleomycin injury

Am J Respir Crit Care Med

Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome

Cochrane Database Syst Rev

Molecular diversity and function of K+ channels in airway and alveolar epithelial cells

Am J Physiol Lung Cell Mol Physiol

Sepsis impairs alveolar epithelial function by downregulating Na-K-ATPase pump

Am J Physiol Lung Cell Mol Physiol

Pulmonary surfactant: an immunological perspective

Cell Physiol Biochem

Interstitial lung diseases in children

Orphanet J Rare Dis

Patterning and plasticity in development of the respiratory lineage

Dev Dyn

Alveolar epithelial type II cell: defender of the alveolus revisited

Respir Res

Molecular and cellular characteristics of ABCA3 mutations associated with diffuse parenchymal lung diseases in children

Hum Mol Genet

Mechanisms of neutrophil transmigration across the vascular endothelium in COPD

Thorax

Cell-based therapies for lung disease

Br Med Bull

New surfactant protein C gene mutations associated with diffuse lung disease

J Med Genet

Cells in focus
Alveolar epithelial cells: Master regulators of lung homeostasis