ANCA Autoimmunity Inflammation NETs Thrombomodulin Vasculitis
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摘要

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing vasculitis with the presence of pathogenic ANCA. ANCA can potentially cause neutrophil activation and induce neutrophil extracellular traps (NETs), resulting in endothelial damage as well as activation of autoreactive B cells and alternative complement pathway. Recombinant thrombomodulin (rTM) protects the endothelium from vascular injury during disseminated intravascular coagulation, thus we hypothesized that rTM ameliorates necrotizing vasculitis in AAV. In this study, rTM was administered in an experimental AAV rat model. Treatment of experimental AAV rats with rTM improved pulmonary hemorrhage and glomerulonephritis, with a suppression of ANCA production and NETs formation. In addition, in vitro experiments showed that rTM bound to neutrophils via Mac-1 (macrophage-1 antigen) and inhibited ANCA-induced NETs formation accompanied by a suppression of histone citrullination, leading to a protection of the endothelium from NETs toxicity. Additionally, rTM affected lymphocytes leading to the inhibition of pro-inflammatory cytokine/chemokin in PBMC during the antibody production process, which might indirectly be involved in the reduction of pathogenic ANCA. Our data revealed that the rTM could ameliorate autoimmune vasculitis through a combination of different biological mechanisms.

译文

抗中性粒细胞胞浆抗体 (ANCA) 相关性血管炎 (AAV) 以坏死性血管炎为特征,存在致病性 ANCA。ANCA 可以潜在地引起中性粒细胞活化并诱导中性粒细胞细胞外陷阱 (NETs),导致内皮损伤以及自身反应性 b细胞和替代补体途径的活化。重组血栓调节蛋白 (rTM) 在弥散性血管内凝血时保护内皮免受血管损伤,因此我们假设 rTM 改善 AAV 中的坏死性血管炎。在本研究中,rTM 是在实验性 AAV 大鼠模型中进行的。RTM 治疗实验性 AAV 大鼠改善了肺出血和肾小球肾炎,抑制了 ANCA 的产生和 NETs 的形成。此外,体外实验表明 rTM 通过 Mac-1 (巨噬细胞-1 抗原) 与中性粒细胞结合,并抑制 ANCA 诱导的 NETs 形成,同时抑制组蛋白瓜氨酸化, 导致保护内皮免受 NETs 毒性。此外,在抗体产生过程中,rTM 影响淋巴细胞,导致 PBMC 中促炎细胞因子/趋化因子的抑制,这可能间接参与致病性 ANCA 的减少。我们的数据显示,rTM 可以通过不同生物学机制的结合改善自身免疫性血管炎。

vasculitis

免疫 血管炎 疾病
概述  :  

血管炎(vasculitis)是指血管发生的炎症反应,导致血管壁增生、脆弱、狭窄或瘢痕化。此类变化可能会限制血液流动,并损害相应的器官和组织。根据各自的成因,部分类型血管炎可能仅影响某个局部器官,其他类型的血管炎则可能影响全身多个器官。血管炎的临床特征也有极大的差异,部分血管炎为短期、自限性,即使未经治疗,也会逐渐自行消退;还有部分则呈现慢性炎症反应,必须采取药物治疗以控制炎症、预防病情急性发作。   分类 目前最为众人

vasculitis  英/,væskjʊ'laitis/ 美/,væskjə'laitis/

释义    n. [内科] 血管炎;结节性脉管炎

例句    This pattern of lesion distribution might help to differentiate NBS from other vasculitides as well as from the inflammatory-demyelinating diseases of the CNS, such as MS.这种病变分布模式可能有助于将NBS与其他血管炎药物以及中枢神经系统的炎性脱髓鞘疾病(如MS)区分开来。

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