Mast cell proteases as protective and inflammatory mediators.
Mast cell proteases as protective and inflammatory mediators.
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DOI：
10.1007/978-1-4419-9533-9_12
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发表时间：
2011
影响因子：
--
通讯作者：
Caughey, George H.
中科院分区：
文献类型：
--
作者：
Caughey, George H.
蛋白酶是由肥大细胞产生的最丰富的一类蛋白质。其中许多储存在膜封闭的细胞内颗粒中，直到通过脱粒刺激释放，其中包括通过与多价过敏原结合的IgE交联高亲和力IgE受体FcεRI。理解和分离蛋白酶的功能是重要的，因为在不同组织位置的肥大细胞中表达不同。实验室动物和人类之间蛋白酶表达的差异也影响在肥大细胞功能的动物模型中获得的结果可以外推到人类的置信度。肥大细胞蛋白酶的致炎潜力是其生物学研究的第一个方面，并受到了最多的关注，部分原因是它们中的一些-特别是胰蛋白酶和食糜酶-是局部和全身肥大细胞脱粒和过敏反应的生物标志物。虽然一些蛋白酶确实会增加过敏性炎症，并且是治疗哮喘和相关过敏性疾病的潜在抑制靶点，但它们在某些情况下具有保护性甚至抗炎性。例如，肥大细胞类胰蛋白酶可以防止严重的细菌性肺部感染，并可以限制皮肤中血管舒张神经肽引起的炎症的“发红”成分。糜酶有助于维持肠道屏障功能和驱逐寄生蠕虫，并可通过产生血管紧张素II来支持过敏反应期间的血压。在其他生死攸关的例子中，羧肽酶A3和其他肥大细胞肽酶限制了内源性肽如脓毒性腹膜炎期间的内皮素和神经降压素以及蛇毒相关肽的全身毒性。另一方面，肥大细胞肽酶介导的保护性细胞因子（如IL-6）的破坏可增加脓毒症的死亡率。从肥大细胞释放的肽酶也影响非肥大细胞蛋白酶，例如通过激活基质金属蛋白酶级联，其在对感染的应答和组织损伤的消退中是重要的。总体而言，肥大细胞蛋白酶具有多种作用-炎症和抗炎，保护性和免疫性-与肥大细胞在变态反应，组织稳态和先天免疫中日益受到重视的贡献保持一致。
Proteases are the most abundant class of proteins produced by mast cells. Many of these are stored in membrane-enclosed intracellular granules until liberated by degranulating stimuli, which include cross-linking of high affinity IgE receptor FcεRI by IgE bound to multivalent allergen. Understanding and separating the functions of the proteases is important because expression differs among mast cells in different tissue locations. Differences between laboratory animals and humans in protease expression also influence the degree of confidence with which results obtained in animal models of mast cell function can be extrapolated to humans. The inflammatory potential of mast cell proteases was the first aspect of their biology to be explored and has received the most attention, in part because some of them—notably tryptases and chymases—are biomarkers of local and systemic mast cell degranulation and anaphylaxis. Although some of the proteases indeed augment allergic inflammation and are potential targets for inhibition to treat asthma and related allergic disorders, they are protective and even anti-inflammatory in some settings. For example, mast cell tryptases may protect from serious bacterial lung infections and may limit the “rubor” component of inflammation caused by vasodilating neuropeptides in the skin. Chymases help to maintain intestinal barrier function and to expel parasitic worms, and may support blood pressure during anaphylaxis by generating angiotensin II. In other life-or-death examples, carboxypeptidase A3 and other mast cell peptidases limit systemic toxicity of endogenous peptides like endothelin and neurotensin during septic peritonitis, and inactivate venom-associated peptides. On the other hand, mast cell peptidase-mediated destruction of protective cytokines, like IL-6, can enhance mortality from sepsis. Peptidases released from mast cells also influence non-mast cell proteases, such as by activating matrix metalloproteinase cascades, which are important in responses to infection and resolution of tissue injury. Overall, mast cell proteases have a variety of roles—inflammatory and anti-inflammatory, protective and deleterious—in keeping with the increasingly well-appreciated contributions of mast cells in allergy, tissue homeostasis, and innate immunity.
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影响因子：
15.9
作者：
Blair, RJ;Meng, H;Gruber, BL
通讯作者：
Gruber, BL
影响因子：
15.3
作者：
BRIGGAMAN, RA;SCHECHTER, NM;LAZARUS, GS
通讯作者：
LAZARUS, GS
影响因子：
30.5
作者：
Corry, DB;Rishi, K;Kheradmand, F
通讯作者：
Kheradmand, F
影响因子：
64.8
作者：
Cocks, TM;Fong, B;Moffatt, JD
通讯作者：
Moffatt, JD
DOI：
10.1007/bf02899101
发表时间：
1989-01-01
期刊：
VIRCHOWS ARCHIV B-CELL PATHOLOGY INCLUDING MOLECULAR PATHOLOGY
影响因子：
--
作者：
BALAZS, M;ILLYES, G;VADASZ, G
通讯作者：
VADASZ, G