Extracellular alveolar proteasome: possible role in lung injury and repair

The ubiquitin-proteasome system is the major intracellular pathway for protein degradation in eukaryotes, and it also generates oligopeptides for antigen presentation. However, the 20S proteasome is also associated with the cell's outer membrane, and observations indicate its physiologic presence and biological activity in the extracellular alveolar space (i.e., in the epithelial lining fluid). Furthermore, its concentration is increased in the adult respiratory distress syndrome, acute lung injury, and other inflammatory lung disease. While its cellular origin, potential extracellular biological role, and mechanisms for extracellular transport are hitherto unclear, extracellular alveolar proteasomes could have a role in protein clearance, digestion of alveolar debris, modification or activation of secreted precursor proteins, and/or antigen processing, both in health and lung disease. This article summarizes available information on the extracellular alveolar proteasome and its possible role in alveolar maintainance, lung injury, and repair.