Serum tryptase and the laboratory diagnosis of systemic mastocytosis

Trypsinlike activity was first associated with human mast cells by histoenzymatic stains.(10, 25, 28) Abundant and releasable trypsinlike activity was found in human lung-derived mast cells in 1981.(82) This discovery was followed by purification to homogeneity of the enzyme accounting for more than 90% of this activity; this enzyme was named tryptase.(81) The enzyme was found to be a tetramer that spontaneously and irreversibly reverted to inactive monomers at neutral pH in a physiologic salt solution unless stabilized by heparin or dextran sulfate.(2,78) In 1998, the crystal structure of lung-derived tryptase was determined,(69) confirming the tetrameric structure and the length of the heparin-binding groove previously predicted.(2) Two heparin grooves were found in each tetramer, each groove spanning the two adjacent subunits bound to one another only through weak hydrophobic interactions. All the active sites faced into the small, central pore of the planar tetramer, thereby restricting inhibitor (and substrate) access.' Because tryptase is selectively concentrated in mast cell secretory granules, it has also been studied as a clinical marker of mast cell-mediated diseases. This article reviews the molecular and biochemical biology of the human mast cell tryptase gene family and then considers the use of tryptase as a marker for systemic mastocytosis and systemic anaphylaxis.