Proteases are enzymes that have the capacity to hydrolyze peptide bonds and degrade other proteins. They are classified according to the active groups of their catalytic center. In lung disease, the three major protease groups of interest are serine, cysteine, and the matrix metalloproteases (MMPs)(1). Another group is the ADAM (“a disintegrin and metalloprotease”) family of proteases, which has an emerging role in mucin production and cytokine processing (2). We direct the reader to some of the many excellent reviews on the structural and functional aspects of the serine, cysteine, and MMP families and their cognate inhibitors (3–5).

The major sources of proteases within the lung are inffammatory cells, such as neutrophils, mast cells, macrophages, and lymphocytes (6–8). Other cells, including epithelial, endothelial, and fibroblasts, also synthesize proteases (9, 10). Serine proteases, including neutrophil elastase (NE), cathepsin G, and proteinase 3, are packaged in primary granules within neutrophils (11). Some of the metalloproteases, MMP-8 and MMP-9, are also packaged into specific and gelatinase granules, respectively, in the neutrophil (12). Neutrophil proteases are released either intracellularly into phagolysosomes or extracellularly after cellular activation (13). Differentiation of monocytes to macrophages results in the loss of the serine protease complement of these cells. However, this is replaced by an ability to synthesize other proteases, including a number of MMPs and elastolytic cathepsins (7).