Mast cells are now recognized as key players in diverse pathologies, but the mechanisms by which they contribute in such settings are only partially understood. Mast cells are packed with secretory granules, and when they undergo degranulation in response to activation the contents of the granules are expelled to the extracellular milieu. Chymases, neutral serine proteases, are the major constituents of the mast cell granules and are hence released in large amounts upon mast cell activation. Following their release, chymases can cleave one or several of a myriad of potential substrates, and the cleavage of many of these could potentially have a profound impact on the respective pathology. Indeed, chymases have recently been implicated in several pathological contexts, in particular through studies using chymase inhibitors and by the use of chymase-deficient animals. In many cases, chymase has been shown to account for mast cell-dependent detrimental effects in the respective conditions and is therefore emerging as a promising drug target. On the other hand, chymase has been shown to have protective roles in other pathological settings. More unexpectedly, chymase has also been shown to control certain homeostatic processes. Here, these findings are reviewed.
J Innate Immun

中文翻译：

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肥大细胞糜蛋白酶的体内功能的新颖见解：敲除和抑制剂的经验教训。

肥大细胞现在被认为是多种病理学中的关键因素，但是它们在这种情况下所起的作用机制仅被部分理解。肥大细胞中充满了分泌性颗粒，当它们响应激活而进行脱粒时，颗粒的内容物被排出到细胞外环境中。乳糜中性丝氨酸蛋白酶是肥大细胞颗粒的主要成分，因此在肥大细胞活化后会大量释放。乳糜释放后，可以裂解多种潜在底物中的一种或几种，裂解其中的许多底物可能会对各自的病理学产生深远的影响。确实，乳糜病最近与几种病理情况有关，特别是通过使用糜酶抑制剂的研究以及使用糜酶缺乏的动物进行的研究。在许多情况下，糜蛋白酶已显示出在相应条件下肥大细胞依赖的有害作用，因此正成为有希望的药物靶标。另一方面，已证明糜酶在其他病理环境中具有保护作用。更出乎意料的是，糜蛋白酶还被证明可以控制某些体内平衡过程。在这里，对这些发现进行了回顾。糜蛋白酶还被证明可以控制某些体内平衡过程。在这里，对这些发现进行了回顾。糜蛋白酶还被证明可以控制某些体内平衡过程。在这里，对这些发现进行了回顾。
免疫学杂志