Mast cell tryptase, a potent inflammatory mediator, requires heparin for enzymatic activation
Mast cell tryptase, a tetrameric serine protease stored in mast cell granules in complex with heparin proteoglycan or chondroitin sulphate proteoglycan, is an important effector molecule in inflammatory reactions like allergies and asthma. In this study we have investigated the requirements for acti...
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| Formato: | L3 |
| Lenguaje: | Inglés sueco |
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SLU/Dept. of Molecular Biosciences
2007
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| Sumario: | Mast cell tryptase, a tetrameric serine protease stored in mast cell granules in complex with heparin proteoglycan or chondroitin sulphate proteoglycan, is an important effector molecule in inflammatory reactions like allergies and asthma. In this study we have investigated the requirements for activation of human βI-tryptase and βII-tryptase, the major tryptases of human mast cells. βI-tryptase and βII-tryptase differ in only one amino acid, no. 102, where βI-tryptase has an asparagine (Asn) residue which is also site for glycosylation while βII-tryptase has a lysine (Lys) residue and lacks glycosylation at that site. We found that both βI-tryptase and βII-tryptase were dependent on heparin for activation and that optimal activity for βI-tryptase occurred at acidic pH while activation of βII-tryptase was less pH-dependent. Both βI-tryptase and βII-tryptase had a strong affinity for heparin-Sepharose at acidic pH but this affinity decreased at neutral pH. The β-tryptases both showed a bell shaped dose response curve for heparin induced activity. These results, taken together with results from a parallel study indicate an important role for heparin in the activation of human β-tryptase. |
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