Genetic insights into mast cell chymase and tryptase function

Summary As the major secreted proteins of degranulating mast cells, chymases and tryptases have long been suspected to be perpetrators of pathology in asthma and other forms of allergic disease. Indeed, the preponderance of evidence now suggests that these enzymes, collectively, are guilty. However, confusion remains over which are most culpable and which of them produce what kinds of pathology. This confusion has several causes, including daunting, nonsystematic nomenclatures, unexplained multiplicities of closely related genes in animal models of allergic disease, uncertainty over which genes deserve to be labelled ‘pseudo’, perplexing allelic relationships and, until recently, a shortage of data correlating enzyme structure with function. Fortunately, recent developments bring these elements into sharper focus. This brief review summarizes some of these developments and discusses how they help to identify the enzymes likely to be important in allergic disease.