Regulation and Physiological Roles of Human Tryptase in the Secretary Granules of Mast Cells

人类胰蛋白酶家族在肥大细胞中选择性表达。β-Tryptase基因(S)的产物在肝素蛋白多糖的存在下，在酸性pH下被自动催化从前‘酶到前’酶，在酸性pH下被二肽基肽酶I自动催化从前‘酶到成熟肽，在酸性pH下通过自发构象变化而被酶活性四聚体催化。Β-类胰蛋白酶在酸性pH条件下由肝素稳定，对丝氨酸蛋白酶的生物抑制剂具有抗性。在没有肝素的情况下，β-类胰蛋白酶在中性pH下形成单体时会自发失活，而在酸性pH下，在有和没有肝素的情况下，不活跃的单体都会自发地重新形成活性四聚体。四聚体形成和再激活的最适pH约为6，提示His残基起着关键作用。这种酶的这些物理化学性质是否与它在体内的调控方式有关尚不确定。在这一点上，人β-类胰蛋白酶被发现具有最适的酸性pH，对肝素蛋白多糖和C3的切割以及自动加工都是最适的。这一特性可能会将体内的最佳活性限制在pH值为酸性的组织或粘膜部位，如炎症和伤口愈合部位，或如呼吸道。人β-类胰蛋白酶的重新激活是发生在细胞外还是细胞内，在体内的pH是酸性的，应该被考虑。

The human tryptase family is selectively expressed in mast cells. Products of β-tryptase gene (s) are autocatalytically processed from the pro- to the pro' enzyme at acidic pH in the presence of heparin proteoglycan, from the pro' to the mature peptide at acidic pH by dipeptidyl peptidase I, and to the enzymatically active tetramer by spontaneous conformational alterations at acidic pH in the presence of heparin. Β-Tryptase is stabilized at acidic pH by heparin, and is resistant to biologic inhibitors of serine proteases. In the absence heparin, β-tryptase spontaneously inactivates at neutral pH as it forms monomers, while at acidic pH the inactive monomers spontaneously re-form the active tetramer both in the presence and in the absence of heparin. The optimal pH for tetramer formation and reactivation is about 6, sugessting His residues play a critical role. Whether these physicochemical properties of the enzyme relate to how it is regulated in vivo is uncertain. In this regard, human β-tryptase was found to have an acidic pH optimum for cleavage of heparin proteoglycan and C3, as well as for autoprocessing. This property might restrict optimal activity in vivo to tisse or mucosal sites with an acidic pH, such as sites of inflammation and wound healing, or such as the airway. Whether reactivation of human β-tryptase occurs at extracellular or intracellular sites, where the pH is acidic in vivo, should be considered.