Oligomerization State of SP-C Involved in Membrane Fragmentation and Innate Defense

Abstract

Pulmonary surfactant is a lipoprotein complex at the bronchoalveolar air-liquid interface, essential to lower surface tension avoiding lung collapse during breathing. Moreover, it also plays an important function in lung defense not only acting as a physical barrier but also actively participating in innate defense mechanisms upon interaction with pathogens and cellular components of the immune system, especially alveolar macrophages. The surfactant protein C (SP-C) is a membrane protein, very hydrophobic, essential for the biophysical properties of pulmonary surfactant. SP-C has also been related with a response to lipopolysaccharide (LPS) in inflammation. Recently it was proposed that both the C-terminal and N-terminal segments of SP-C are able to promote protein-protein interactions, which could progressively induce clustering of SP-C at high densities, a progressive increase in surfactant membrane curvature, and ultimately the SP-C-promoted segregation of small lipoprotein vesicles. The oligomerization state of SP-C and the activity of this protein to fragment membranes has been studied in the context of the effect of SP-C in LPS clearance and in modulating LPS-triggered alveolar macrophages responses, as a first step to understand the challenging participation of surfactant proteins in alveolar homeostasis.