Surfactant-associated protein A is important for maintaining surfactant large-aggregate forms during surface-area cycling.

Alveolar surfactant can be separated into two major subfractions, the large surfactant aggregates (LAs) and the small surfactant aggregates (SAs). The surface-active LAs are the metabolic precursors of the inactive SAs. This conversion of LAs into SAs can be studied in vitro using a technique called surface-area cycling. We have utilized this technique to examine the effect of trypsin on aggregate conversion. Our results show that trypsin increases the conversion of LAs into SAs in a concentration- and time-dependent manner. Immunoblot analysis revealed that surfactant-associated Protein A (SP-A) was the main target of trypsin. To examine further the role of SP-A in aggregate conversion, we tested the effect of Ca2+ and mannan on this process. The absence of Ca2+ (l mM EDTA) and the presence of mannan both increased the formation of SAs. Electron microscopy revealed that highly organized multilamellar and tubular myelin structures were present in samples that converted slowly to SAs. We concluded that SP-A is important for maintaining LA forms during surface-area cycling by stabilizing tubular myelin and multilamellar structures.