Surfactant Protein B Deficiency Induced High Surface Tension: Relationship between Alveolar Micromechanics, Alveolar Fluid Properties and Alveolar Epithelial Cell Injury

Nina Rühl,Bradford J Smith,Lars Knudsen,Matthias Ochs,Timothy E Weaver,Karolin Albert,Elena Lopez-Rodriguez

doi:10.3390/ijms20174243

Abstract

High surface tension at the alveolar air-liquid interface is a typical feature of acute and chronic lung injury. However, the manner in which high surface tension contributes to lung injury is not well understood. This study investigated the relationship between abnormal alveolar micromechanics, alveolar epithelial injury, intra-alveolar fluid properties and remodeling in the conditional surfactant protein B (SP-B) knockout mouse model. Measurements of pulmonary mechanics, broncho-alveolar lavage fluid (BAL), and design-based stereology were performed as a function of time of SP-B deficiency. After one day of SP-B deficiency the volume of alveolar fluid V(alvfluid,par) as well as BAL protein and albumin levels were normal while the surface area of injured alveolar epithelium S(AEinjure,sep) was significantly increased. Alveoli and alveolar surface area could be recruited by increasing the air inflation pressure. Quasi-static pressure-volume loops were characterized by an increased hysteresis while the inspiratory capacity was reduced. After 3 days, an increase in V(alvfluid,par) as well as BAL protein and albumin levels were linked with a failure of both alveolar recruitment and airway pressure-dependent redistribution of alveolar fluid. Over time, V(alvfluid,par) increased exponentially with S(AEinjure,sep). In conclusion, high surface tension induces alveolar epithelial injury prior to edema formation. After passing a threshold, epithelial injury results in vascular leakage and exponential accumulation of alveolar fluid critically hampering alveolar recruitability.

Highlights

The intra-alveolar surfactant is a mixture of 90% lipids and 10% proteins including surfactant proteins which are produced, stored and secreted by alveolar epithelial type 2 (AE2) cells [1]
While hysteresis in Dox off d1 was significantly increased compared to doxycycline containing food (Dox on) this was not the case considering Dox off d3
Dox off d3 was characterized by an even more dramatic reduction in Inspiratory capacity (IC) compared to Dox on and Dox off d1 (Figure 1C)

Summary

Introduction

The intra-alveolar surfactant is a mixture of 90% lipids (mainly phospholipids) and 10% proteins including surfactant proteins which are produced, stored and secreted by alveolar epithelial type 2 (AE2) cells [1]. Among the protein component the hydrophobic surfactant proteins B (SP-B) and C (SP-C) are both of high relevance for the surface tension lowering properties of alveolar surfactant at the air-liquid interface within the alveolar space. Underneath this interface, a very thin layer of liquid, referred to as the hypophase, covers the alveolar epithelium [2,3]. This reduction in surface tension is critical to prevent end-expiratory collapse of distal airspaces and to reduce the work of breathing. SP-B, due to its properties to generate phospholipid membrane-membrane contacts, has been suggested to be involved in the formation and stabilization of surface active films so that surface tension lowering properties are critically dependent on the biophysical properties of SP-B [2,8]

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