The Discovery of 1 - Antitrypsin

Alpha1-Antitrypsin (AAT), an acute-phase protein, is the prototypic member of the serpin superfamily and a major inhibitor of serine proteases such as neutrophil elastase and protease 3. As an acute-phase protein, AAT is thought to play an important role in limiting host tissue injury by proteases at sites of inflammation. The clinical importance of AAT is highlighted in individuals with inherited AAT deficiency who exhibit an increased susceptibility to develop chronic inflammatory conditions including chronic obstructive lung disease, liver diseases and, sometimes, systemic vasculitis and necrotising panniculitis. Recent findings highlight the potential involvement of AAT in several proteolytic pathways and also indicate that it has broader antiprotease activities than previously anticipated. AAT may also exhibit antiinflammatory activities independent of its protease inhibitor function, which suggests the existence of receptor-mediated AAT intracellular internalisation, and provides further evidence of a broad protective role of AAT against not only lung, but also other organ injury.