Neutrophil Elastase and Chronic Lung Disease.
Neutrophil Elastase and Chronic Lung Disease.
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DOI：
10.3390/biom11081065
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发表时间：
2021-07-21
期刊：
影响因子：
5.5
通讯作者：
Shinbashi M
中科院分区：
文献类型：
--
作者：
Voynow JA;Shinbashi M
神经弹性蛋白酶（NE）是由中性粒细胞释放的主要炎性蛋白酶，并且存在于患有囊性纤维化（CF）、慢性阻塞性肺病、非CF支气管扩张和支气管肺发育不良的患者的气道中。虽然NE促进白细胞迁移到感染部位，并且是清除革兰氏阴性菌所必需的，但在慢性炎性气道疾病中，当释放到气道环境中时，它也激活炎症。NE暴露诱导气道重塑，粘蛋白表达和分泌增加，纤毛运动受损。NE通过促进细胞凋亡和衰老来中断上皮修复，并且其通过增加细胞因子表达和释放来直接激活炎症，并且通过触发细胞外陷阱释放和外泌体释放来间接激活炎症，所述细胞外陷阱释放和外泌体释放放大气道中的蛋白酶活性和炎症。NE通过消化调理素和调理素受体、降解先天免疫蛋白如乳铁蛋白和抑制巨噬细胞吞噬作用来抑制先天免疫功能。重要的是，NE导向疗法尚未有效预防NE暴露的病理后遗症，但正在开发新的疗法，提供直接的抗蛋白酶活性和多功能抗炎特性。
Neutrophil elastase (NE) is a major inflammatory protease released by neutrophils and is present in the airways of patients with cystic fibrosis (CF), chronic obstructive pulmonary disease, non-CF bronchiectasis, and bronchopulmonary dysplasia. Although NE facilitates leukocyte transmigration to the site of infection and is required for clearance of Gram-negative bacteria, it also activates inflammation when released into the airway milieu in chronic inflammatory airway diseases. NE exposure induces airway remodeling with increased mucin expression and secretion and impaired ciliary motility. NE interrupts epithelial repair by promoting cellular apoptosis and senescence and it activates inflammation directly by increasing cytokine expression and release, and indirectly by triggering extracellular trap release and exosome release, which magnify protease activity and inflammation in the airway. NE inhibits innate immune function by digesting opsonins and opsonin receptors, degrading innate immune proteins such as lactoferrin, and inhibiting macrophage phagocytosis. Importantly, NE-directed therapies have not yet been effective in preventing the pathologic sequelae of NE exposure, but new therapies are being developed that offer both direct antiprotease activity and multifunctional anti-inflammatory properties.
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DOI：
10.1126/science.1223012
发表时间：
2012-08-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Button B;Cai LH;Ehre C;Kesimer M;Hill DB;Sheehan JK;Boucher RC;Rubinstein M
通讯作者：
Rubinstein M
影响因子：
5.8
作者：
Boxio R;Wartelle J;Nawrocki-Raby B;Lagrange B;Malleret L;Hirche T;Taggart C;Pacheco Y;Devouassoux G;Bentaher A
通讯作者：
Bentaher A
影响因子：
4.8
作者：
Bergin, David A.;Greene, Catherine M.;McElvaney, Noel G.
通讯作者：
McElvaney, Noel G.
影响因子：
3.5
作者：
Devaney, JM;Greene, CM;McElvaney, NG
通讯作者：
McElvaney, NG
影响因子：
5.3
作者：
Bruscia EM;Bonfield TL
通讯作者：
Bonfield TL