The role of proteases and anti-proteases in tissue damage. A complex balance exists between proteases and anti-proteases that determines the presence and extent of connective tissue damage. The interplay is made more complex by interactions between various molecules. As well as being inactivated by AAT, neutrophil elastase is also inhibited by SERPINA3 and SLPI. However, neutrophil elastase has the ability to inhibit TIMP1-4 (inhibitors of MMPs) and MMPs can inactivate AAT. This complex interaction of activation/inactivation means that interpreting the balance of proteases and anti-proteases is far from straight forward. AAT, α1-antitrypsin; MMPs, matrix metalloproteinases; SERPINA3, serine protease inhibitor gene; SLPI, secretory leucocyte protease inhibitor; TIMP, tissue inhibitors of metalloproteinase.