Human Mast Cell β-Tryptase Is a Gelatinase

Abstract

Remodeling of extracellular matrix is an important component in a variety of inflammatory disorders as well as in normal physiological processes such as wound healing and angiogenesis. Previous investigations have identified the various matrix metalloproteases, e.g., gelatinases A and B, as key players in the degradation of extracellular matrix under such conditions. Here we show that an additional enzyme, human mast cell β-tryptase, has potent gelatin-degrading properties, indicating a potential contribution of this protease to matrix degradation. Human β-tryptase was shown to degrade gelatin both in solution and during gelatin zymographic analysis. Further, β-tryptase was shown to degrade partially denatured collagen type I. β-Tryptase bound strongly to gelatin, forming high molecular weight complexes that were stable during SDS-PAGE. Mast cells store large amounts of preformed, active tryptase in their secretory granules. Considering the location of mast cells in connective tissues and the recently recognized role of mast cells in disorders in which connective tissue degradation is a key event, e.g., rheumatoid arthritis, it is thus likely that tryptase may contribute to extracellular matrix-degrading processes in vivo.

Comparison of Mast Cells and Inflammatory Cells within Periapical Lesions and Comparison of Degranulated Mast Cells Between Fibrous and Inflamed Area in Radicular Cysts: An Immunohistochemical Study

“…Mast cells are reported to specifically influence granulation tissue organization during wound repair [5]. All these findings support the fact that degranulation promotes fibrosis but at the same time other products of degranulation such as tryptase also play a role in the degradation of connective tissue [11]. Thus, the increase in collagen detected after tryptase treatment must reflect an increase in the net biosynthetic rate of type I collagen.…”

Tryptase-positive mast cells correlate with angiogenesis in early breast cancer patients

“…Blair et al have demonstrated that direct addition of tryptase to microvascular endothelial cells cultured on Matrigel caused a pronounced increase of capillary growth, which was suppressed by specific tryptase inhibitors, and directly induced endothelial cell proliferation in a dose-dependent fashion (10). Tryptase is involved in tissue remodelling and it may also act indirectly on tissue neovascularization by releasing latent angiogenetic factors bound to the extracellular matrix (27). Tryptase is an agonist of the proteinase-activated receptor-2 (PAR-2) in vascular endothelial cells and breast cancer cells (28)(29)(30)(31)(32)(33).…”

Mast Cell-Mediated Remodeling and Fibrinolytic Activity Protect against Fatal Glomerulonephritis

“…Lipid mediators such as LTC4, as well as certain cytokines such as IL-4, TNF-␣, and TGF-␤ also favor the growth of fibroblasts (69,70). Conversely, mast cell proteases such as tryptase were also found to have potent proteolytic activity toward denatured collagen or gelatin (71). Similarly, mast cell chymase has been described to activate matrix metalloproteinases 2 and 9, which also degrade denatured collagen, either by activating their proform or by degrading their natural inhibitor protein tissue inhibitor of metalloproteinase (72,73).…”