Surfactant Protein C (SP-C) deficiency caused by SFTPC mutations is considered in the technical literature to be a frequently described cause of familial types of interstitial lung diseases, which can manifest themselves in diverse ways. The certainly most well-known and researched entity of the fibrotic lung diseases here is idiopathic pulmonary fibrosis (IPF), for the development of which mutations in the SFTPC gene normally show a high penetrance. In my doctoral thesis, I was able to work out that SP-C in vivo plays a decisive role both for the pulmonary surfactant metabolism as well as its function with regard to the pulmonary micromechanics. In addition, the study was able to demonstrate the age-related effects of a lack of SP-C on the pulmonary structure-function relationship in the early stages of fibrotic remodeling. This leads to the development of a complex murine disease phenotype, characterized by a progressive pseudo-emphysematous increase in air space, impaired pulmonary cholesterol homeostasis and altered plasticity of the local macrophages. These findings underline the existence of a profibrotic, immune mechanical reciprocal axis between altered acinar micromechanics and local immune cells, which occurs at the start of a chronic remodeling process, in the final stages of which a fibrotic remodeling of the murine lung occurs.
Text: AZ / J. Ruwisch
Photo: R. Ruwisch