Roles of mast cell proteases in airways.

The mast cell proteases tryptase and chymase have long been known to constitute one-fifth of the total protein in mast cells. However, their biological functions have not been easy to study because of the difficulty in obtaining sufficient amounts of the enzymes to study their biological functions. Recently, we have been fortunate to have available a permanent line of dog mastocytoma cells to purify both enzymes to homogeneity, and we have used the purified enzymes in two ways. First, in a series of biological studies, we have discovered unique and potent actions of the enzymes that may provide important insights into the pathogenesis of diseases such as asthma and cystic fibrosis. Important biological activities are also likely to exist in other tissues. Because of their structures, mast cell proteases are likely to act in proximity to their sites of release. Thus, the presence and amounts of tryptase and chymase in specific loci may play important roles in tissue responses. In diseases such as asthma and cystic fibrosis, there is evidence that the expression of these mast cell enzymes changes, and these changes have important pathogenetic implications. Second, we have begun to perform structural studies of the enzymes. The recent cloning of tryptase by our group should assist in the better understanding of its functions. Crystallography of the pure proteins should provide further insights and could be the basis of rational development of potent and selective drugs that will inhibit their actions.