Section of Pulmonary and Critical Care Medicine, Medicine Service, Veterans Affairs Medical Center, Mailstop 111-D, 4150 Clement Street, San Francisco, CA 94121, USA.
Am J Respir Cell Mol Biol. 2010 Mar;42(3):257-67. doi: 10.1165/rcmb.2009-0324RT. Epub 2009 Nov 20.
Mast cells make and secrete an abundance of peptidases, which are stored in such large amounts in granules that they comprise a high fraction of all cellular protein. Perhaps no other immune cell is so generously endowed with peptidases. For many years after the main peptidases were first described, they were best known as markers of degranulation, for they are released locally in response to mast cell stimulation and can be distributed systemically and detected in blood. The principal peptidases are tryptases, chymases, carboxypeptidase A3, and dipeptidylpeptidase I (cathepsin C). Numerous studies suggest that these enzymes are important and even critical for host defense and homeostasis. Endogenous and allergen or pathogen-associated targets have been identified. Belying the narrow notion of peptidases as proinflammatory, several of the peptidases limit inflammation and toxicity of endogenous peptides and venoms. The peptidases are interdependent, so that absence or inactivity of one enzyme can alter levels and activity of others. Mammalian mast cell peptidases--chymases and tryptases especially--vary remarkably in number, expression, biophysical properties, and specificity, perhaps because they hyper-evolved under pressure from the very pathogens they help to repel. Tryptase and chymase involvement in some pathologies stimulated development of therapeutic inhibitors for use in asthma, lung fibrosis, pulmonary hypertension, ulcerative colitis, and cardiovascular diseases. While animal studies support the potential for mast cell peptidase inhibitors to mitigate certain diseases, other studies, as in mice lacking selected peptidases, predict roles in defense against bacteria and parasites and that systemic inactivation may impair host defense.
肥大细胞产生和分泌大量的肽酶，这些肽酶在颗粒中大量储存，占细胞总蛋白的很大一部分。也许没有其他免疫细胞有如此丰富的肽酶。在最初描述的主要肽酶之后的许多年里，它们作为脱颗粒的标志物而最为人所知，因为它们在肥大细胞刺激时局部释放，并可以在全身分布并在血液中检测到。主要的肽酶是类胰蛋白酶、糜蛋白酶、羧肽酶 A3 和二肽基肽酶 I（组织蛋白酶 C）。许多研究表明，这些酶对宿主防御和内稳态非常重要，甚至是关键的。已经确定了内源性和过敏原或病原体相关的靶标。这些酶不仅是炎症性的，而且有一些还限制了内源性肽和毒液的炎症和毒性，这与肽酶窄义概念相矛盾。这些肽酶相互依赖，因此一种酶的缺失或失活会改变其他酶的水平和活性。哺乳动物肥大细胞肽酶——特别是糜蛋白酶和类胰蛋白酶——在数量、表达、生物物理特性和特异性方面差异显著，这可能是因为它们在抵御自身帮助抵御的病原体的压力下高度进化而来。类胰蛋白酶和糜蛋白酶参与某些病理过程，刺激了治疗性抑制剂的开发，用于哮喘、肺纤维化、肺动脉高压、溃疡性结肠炎和心血管疾病。虽然动物研究支持肥大细胞肽酶抑制剂减轻某些疾病的潜力，但其他研究，如缺乏某些肽酶的小鼠，预测了它们在防御细菌和寄生虫方面的作用，以及全身失活可能会损害宿主防御。
