Alpha-1 Antitrypsin Biology

Alpha-1 antitrypsin (AAT) is an acute phase protein mainly produced by liver. Its main function is to protect lungs from neutrophil elastase, a potent protease that degrades elastin and other connective tissue components. Besides elastase, its spectrum of action extends to many other proteolytic enzymes (including proteinase-3, cathepsin-G, and defensins-α from neutrophils; chymase and tryptase from mast cells; trypsin, chymotrypsin, and elastase from pancreas; granzyme B from T-lymphocytes; and the circulating serine proteases plasmin, thrombin, plasminogen activator 1&2, factor Xa, and kallikreins 7&14), providing to human serum more than 90% of its antiprotease capacity. Incidentally, the neutralization of serine proteases prevents activation of tissue proenzymes, such as metalloproteinases, kallikreins, or cathepsins, as well as the transmembrane protease-activated receptors (PARs) expressed throughout the body, thereby controlling the intensity and resolution of inflammation. In addition, AAT regulates the activity of various key cells of the immune system, such as neutrophils, lymphocytes, monocytes, macrophages, and mast cells, as well as fibroblasts, endothelial, and epithelial cells. These capabilities together provide to AAT multiple antiinflammatory, immunomodulatory, and antimicrobial properties.