Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis

Alejandro Alonso,Jesús Pérez-Gil,Bárbara Olmeda,Olga Cañadas

doi:10.3390/ijms21103708

Abstract

Pulmonary surfactant is a lipid/protein complex synthesized by the alveolar epithelium and secreted into the airspaces, where it coats and protects the large respiratory air–liquid interface. Surfactant, assembled as a complex network of membranous structures, integrates elements in charge of reducing surface tension to a minimum along the breathing cycle, thus maintaining a large surface open to gas exchange and also protecting the lung and the body from the entrance of a myriad of potentially pathogenic entities. Different molecules in the surfactant establish a multivalent crosstalk with the epithelium, the immune system and the lung microbiota, constituting a crucial platform to sustain homeostasis, under health and disease. This review summarizes some of the most important molecules and interactions within lung surfactant and how multiple lipid–protein and protein–protein interactions contribute to the proper maintenance of an operative respiratory surface.

Highlights

In the lung, the essential function of respiration takes place through gas exchange between air and blood
In this review we describe the central role of pulmonary surfactant in different aspects of lung homeostasis, highlighting the importance of lipid–protein and protein–protein interactions in achieving this vital function
This bacteriostatic effect has been related to the ability of SP-A and SP-D to increase the permeability of the microbial cell membrane [264]

Summary

Introduction

The essential function of respiration takes place through gas exchange between air and blood. The presence of an air–water interface physically requires a reduction of the surface tension generated by the cohesive forces between liquid molecules that, otherwise, would lead to shrinkage of alveoli [2] To fulfill this crucial role, alveolar epithelial type II cells (AE2C) secrete pulmonary surfactant, a lipid–protein complex that forms a surface active film at the respiratory interface, allowing its stability and avoiding alveolar collapse during expiration [3,4]. A balance must be accomplished between inflammatory responses necessary to defend the lung against toxins or pathogens and the need of a basal toleration to avoid exacerbated reactions [15] Besides this immune homeostasis, ensuring the availability of a proper amount of surfactant with accurate composition and structure, under several physiological or pathological situations, is essential for stabilizing the respiratory surface and supporting alveolar homeostasis [16]. In this review we describe the central role of pulmonary surfactant in different aspects of lung homeostasis, highlighting the importance of lipid–protein and protein–protein interactions in achieving this vital function

The Essential Role of Pulmonary Surfactant at the Lung Interface

Alteration of the Interfacial Surfactant Film is Cause of Lung Injury

Surfactant Homeostasis in the Alveolar Spaces

Surfactant Structures in the Alveolar Spaces

Surfactant Recycling and Catabolism

Interaction with Bacterial Lipopolysaccharide

Interaction with Pattern-Recognition Receptors

Antimicrobial Effect

Modulation of Apoptosis

Efferocytosis

Tissue Repair

Findings