SP-C deficiency causes early alveolar de-recruitment resulting in a combination of air spaces over-distension and spontaneous fibrotic remodeling in aging lungs

Abstract

Surfactant protein C (SP-C) deficiency has been found in samples from patients suffering from idiopathic pulmonary fibrosis (IPF), especially familial forms of lung fibrosis. Lung surfactant reduces surface tension at the air-liquid alveolar interface, decreasing the work of breathing and avoiding alveolar collapse. SP-C is a small hydrophobic protein providing stability of the lung surfactant film during compression of the interface. In this study we aimed to investigate whether the absence of SP-C may impact the alveolar structure during the mice adult life (from 10 to 60 weeks of age). Alveolar dynamics showed progressive alveolar de-recruitment in aging mice and oxygen saturation was readily impaired at the age of 20 weeks. A closer look into lung structure revealed how the decreasing volume density of alveolar spaces, contributing to non-ventilated parenchyma density, was accompanied by the increase of the ductal counterparts. Moreover, volume weighted volume of alveoli was rapidly increasing leading to re-organization of air-spaces. Lastly, fibrotic wounds can be observed in mice lungs from the age of 50 weeks. In conclusion, SP-C deficiency leads to spontaneous fibrotic development resulting in mild impairment of lung function due to alveolar de-recruitment, re-organization of air-spaces and fibrotic remodeling.