肥大细胞蛋白酶在哮喘中的新作用
2020/02/11
摘要
肥大细胞在哮喘中起关键作用现在已得到确定。多种证据，包括临床研究和对肥大细胞缺陷小鼠的研究，均支持这一观点。但是，我们对于肥大细胞影响哮喘病理的确切效应机制的认识仍然有限。肥大细胞含有大量的分泌颗粒，其中充满了多种生物活性化合物，包括组胺，细胞因子，溶酶体水解酶，丝氨酸蛋白多糖和许多肥大细胞限制性蛋白酶。当肥大细胞被激活时，例如对IgE受体交联作出反应，其颗粒内容物释放到外部，并可能引起大规模的炎症反应。肥大细胞的限制性蛋白酶包括类胰蛋白酶，乳糜酶和羧肽酶A3。它们以非常高的水平表达和储存。现在有新的证据支持这些酶在哮喘病理中的重要作用。然而，有趣的是，肥大细胞的限制性蛋白酶的作用具有多态性，保护性和有害活性并存。在这里总结了有关肥大细胞限制性蛋白酶如何影响哮喘的最新知识。
The emerging role of mast cell proteases in asthma.
Pejler G.et al. Eur Respir J. 2019 Aug 01.
Abstract
It is now well established that mast cells play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on mast cell-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which mast cells influence asthma pathology. Mast cells contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of mast cell-restricted proteases. When mast cells are activated, e.g. in response to IgE receptor crosslinking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The mast cell-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels. There is now emerging evidence supporting a prominent role of these enzymes in the pathology of asthma. Interestingly though, the role of the mast cell-restricted proteases is multifaceted, encompassing both protective and detrimental activities. Here, I review the current knowledge of how the mast cell-restricted proteases impact on asthma.
肥大细胞在哮喘中起关键作用现在已得到确定。多种证据，包括临床研究和对肥大细胞缺陷小鼠的研究，均支持这一观点。但是，我们对于肥大细胞影响哮喘病理的确切效应机制的认识仍然有限。肥大细胞含有大量的分泌颗粒，其中充满了多种生物活性化合物，包括组胺，细胞因子，溶酶体水解酶，丝氨酸蛋白多糖和许多肥大细胞限制性蛋白酶。当肥大细胞被激活时，例如对IgE受体交联作出反应，其颗粒内容物释放到外部，并可能引起大规模的炎症反应。肥大细胞的限制性蛋白酶包括类胰蛋白酶，乳糜酶和羧肽酶A3。它们以非常高的水平表达和储存。现在有新的证据支持这些酶在哮喘病理中的重要作用。然而，有趣的是，肥大细胞的限制性蛋白酶的作用具有多态性，保护性和有害活性并存。在这里总结了有关肥大细胞限制性蛋白酶如何影响哮喘的最新知识。
（中国医科大学附属第一医院 李文扬 摘译 杨冬 审校）
（Pejler G.et al. Eur Respir J. 2019 Aug 01.）
（Pejler G.et al. Eur Respir J. 2019 Aug 01.）
The emerging role of mast cell proteases in asthma.
Pejler G.et al. Eur Respir J. 2019 Aug 01.
Abstract
It is now well established that mast cells play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on mast cell-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which mast cells influence asthma pathology. Mast cells contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of mast cell-restricted proteases. When mast cells are activated, e.g. in response to IgE receptor crosslinking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The mast cell-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels. There is now emerging evidence supporting a prominent role of these enzymes in the pathology of asthma. Interestingly though, the role of the mast cell-restricted proteases is multifaceted, encompassing both protective and detrimental activities. Here, I review the current knowledge of how the mast cell-restricted proteases impact on asthma.
