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  • Title: Modulation of tryptase release from human tonsil mast cells by protease inhibitors.
    Author: He S, Xie H.
    Journal: Pharmacol Rep; 2005; 57(4):523-30. PubMed ID: 16129920.
    Abstract:
    AIM: To examine the influence of protease inhibitors on tryptase release, and as a comparison the influence of the inhibitors on histamine secretion was assessed. METHODS: Enzymatically dispersed cells from human tonsil were challenged with anti-IgE or calcium ionophore A23187 (CI) in the absence or presence of the tryptase and chymase inhibitors, and tryptase and histamine release was determined. RESULTS: IgE-dependent tryptase release from dispersed tonsil mast cells was inhibited by a maximum of approximately 35.5% and 35.7% by N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) and N-tosyl-L-phenylalanyl chloromethyl ketone (TPCK), respectively. The similar degree of inhibition of CI-induced tryptase release was observed also with these two inhibitors. Preincubation of TLCK or TPCK with cells at 37 degrees C for 20 min before addition of the stimulus improved slightly their ability to inhibit anti-IgE and CI-induced tryptase release. Protamine showed dual action on tryptase release from tonsil mast cells. The concentration-dependent inhibition of anti-IgE and CI-induced release of histamine from tonsil mast cells was also observed with TLCK, TPCK and protamine. The maximum inhibition of anti-IgE-induced histamine release was approximately 26.6%, 30.8% and 30.1% with TLCK, TPCK and protamine, respectively. At the concentrations tested, TLCK and TPCK by themselves did not stimulate tryptase and histamine release from tonsil mast cells. CONCLUSION: It was demonstrated that protease inhibitors were able to inhibit IgE-dependent tryptase release from human tonsil mast cells, which suggests strongly that they can be developed to a novel class of anti-inflammatory drugs to treat allergic conditions in man.
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