The roles of neutrophil serine proteinases in idiopathic inflammatory myopathies.
The roles of neutrophil serine proteinases in idiopathic inflammatory myopathies.
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中性粒细胞丝氨酸蛋白酶在特发性炎症性肌病中的作用
DOI：
10.1186/s13075-018-1632-x
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发表时间：
2018-07-05
影响因子：
4.9
通讯作者：
Luo H
中科院分区：
文献类型：
--
作者：
Gao S;Zuo X;Liu D;Xiao Y;Zhu H;Zhang H;Luo H
背景皮肌炎和多发性肌炎是最常见的特发性炎性肌病。典型的组织病理学发现包括炎性细胞浸润到肌肉组织中。中性粒细胞丝氨酸蛋白酶（NSP）是一种颗粒相关酶，通过增加血管内皮细胞的通透性在炎症细胞迁移中发挥作用。本研究旨在探讨NSPs在IIMs发病机制中的作用。分别采用酶联免疫吸附试验、免疫组化和免疫荧光法检测血清和肌肉组织中NSPs的表达。用患者血清培养人真皮微血管内皮细胞（human dermal microvascular endothelial cells，HDMECs），观察患者血清对外周血单个核细胞（peripheral blood mononuclear cells，PBMC）VE-cadherin表达、内皮细胞管形成和跨内皮迁移的影响。这些NSP在患者的PBMC中是低甲基化的。血清NSP与IIM患者的临床指标乳酸脱氢酶、血沉、C反应蛋白、免疫球蛋白G、免疫球蛋白M、免疫球蛋白A呈正相关。抗Jo-1抗体、抗Ro-52抗体或无间质性肺病的患者蛋白酶3水平较低。血清NSP降解的HDMECs的VE-钙粘蛋白，血清NSP的应用增加了HDMECs.ConclusionsOur研究表明，第一次，NSP发挥重要作用，肌肉炎症细胞浸润，通过增加血管内皮细胞的通透性在IIM患者。
BackgroundDermatomyositis and polymyositis are the best known idiopathic inflammatory myopathies (IIMs). Classic histopathologic findings include the infiltration of inflammatory cells into muscle tissues. Neutrophil serine proteinases (NSPs) are granule-associated enzymes and play roles in inflammatory cell migration by increasing the permeability of vascular endothelial cells. In this study, we aimed to find the roles of NSPs in pathogenesis of IIMs.MethodsRNA and DNA were isolated to measure the relative expression of NSPs and their methylation levels. The expression of NSPs in serum and muscle tissues was tested by enzyme-linked immunosorbent assay, immunohistochemistry, and immunofluorescence, respectively. Serum from patients was used to culture the human dermal microvascular endothelial cells (HDMECs), and then we observed the influence of serum on expression of VE-cadherin, endothelial cell tube formation, and transendothelial migration of peripheral blood mononuclear cells (PBMCs).ResultsWe found that the expression of NSPs was increased in PBMCs, serum, and muscle tissues of IIM patients; these NSPs were hypomethylated in the PBMCs of patients. Serum NSPs were positively correlated with clinical indicators of IIM patients, including lactic dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, immunoglobulin G, immunoglobulin M, and immunoglobulin A. Patients with anti-Jo-1, with anti-Ro-52, or without interstitial lung disease had lower levels of proteinase 3. Serum NSPs degraded the VE-cadherin of HDMECs, and serum NSP application increased the permeability of HDMECs.ConclusionsOur studies indicate, for the first time, that NSPs play an important role in muscle inflammatory cell infiltration by increasing the permeability of vascular endothelial cells in IIM patients.
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影响因子：
4
作者：
Dejana, Elisabetta;Orsenigo, Fabrizio;Lampugnani, Maria Grazia
通讯作者：
Lampugnani, Maria Grazia
影响因子：
4.5
作者：
Go DJ;Lee EY;Lee EB;Song YW;Konig MF;Park JK
通讯作者：
Park JK
人类嗜中性粒细胞衍生的组织蛋白酶G和Azurocidin/cap37鉴定为单核细胞和中性粒细胞的趋化剂。
DOI：
10.1084/jem.186.5.739
发表时间：
1997-08-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chertov O;Ueda H;Xu LL;Tani K;Murphy WJ;Wang JM;Howard OM;Sayers TJ;Oppenheim JJ
通讯作者：
Oppenheim JJ
特发性炎症性肌病患者间质性肺病危险因素的临床分析
影响因子：
--
作者：
Cen X;Zuo C;Yang M;Yin G;Xie Q
通讯作者：
Xie Q
DOI：
10.1073/pnas.96.17.9815
发表时间：
1999-08-17
影响因子：
11.1
作者：
Corada, M;Mariotti, M;Dejana, E
通讯作者：
Dejana, E