哮喘联盟

   摘要
   背景:瓜氨酸化目前是一个未被认识的经肽酰基精氨酸脱亚氨酶（PAD）催化蛋白质翻译后修饰的过程。瓜氨酸在新表位的免疫应答在越来越多的炎症和自身免疫性疾病中被发现。然而，高瓜氨酸在支气管哮喘发病机制中的作用仍是未知。
   方法:作为主要的实验工具，我们在对卵清白蛋白致敏和激发的BALB/c 小鼠上检测了2-氯乙酰脒 (2CA)水平--一种PAD 酶抑制剂；它是一种气道变应性炎症的常用模型。 我们还在离体淋巴细胞和细胞系中测定了2CA的水平。
   结果:在体内， 2CA 显著地抑制肺组织的高瓜氨酸化、炎症细胞的浸润和气道-TH 2细胞因子的分泌。2CA 也显著抑制系统性卵清白蛋白特异性和总IgE产生， 在没有显著影响免疫能力的情况下，2CA可有效预防和降低疾病的发生。在体外，在一个有限的激活后阶段，2CA能明显抑制小鼠和人T细胞增殖，阻断细胞周期、诱导细胞凋亡。
   结论:2CA 作为窄谱免疫抑制剂靶向作用于参与活动性炎症病变组织的淋巴细胞群。如果哮喘患者产生高瓜氨酸化，2CA可能成为人类哮喘或过敏性疾病的一种新型的疾病调节剂。
 

（杨冬 审校）
Allergy. 2015 May 13. doi: 10.1111/all.12651. [Epub ahead of print]

 

2-Chloroacetamidine, a novel immunomodulator, suppresses antigen-induced mouse airway inflammation.
 

Maezawa Y1, Paltser G1, Tsui H1, Cheung R1, Wu P1, Nicholas AP2, Dosch HM1.
Author information
 

Abstract
BACKGROUND:Citrullination is a presently under-recognized post-translational protein modification catalyzed by PAD enzymes. Immune responses to citrullinated neo-epitopes are identified in a growing number of inflammatory and autoimmune diseases. However, the involvement of hypercitrullination in the pathogenesis of bronchial asthma is still unknown.
METHODS:As main experimental tool, we examined the effect of 2-Chloroacetamidine (2CA), a PAD enzyme inhibitor, on OVA-immunized and airway-challenged BALB/c mice; a commonly used model of allergic airway inflammation. We also measured the effect of 2CA on ex vivo lymphocytes and cell lines.
RESULTS:In vivo, 2CA dramatically suppressed lung tissue hypercitrullination, inflammatory cell recruitment, and airway-TH 2 cytokine secretion. 2CA also suppressed systemic OVA-specific and total IgE production dramatically, effectively preventing de novo and diminishing established disease without measurably impacting general immunocompetence. In vitro, 2CA markedly inhibited
the proliferation of mouse and human T cells with cell cycle block and apoptosis during a limited, post-activation phase.
CONCLUSIONS:2CA acts as narrow-spectrum immunosuppressant that selectively targets lymphocyte populations involved in active inflammatory tissue lesions. If hypercitrullination is generated in asthmatic patients, 2CA may represent a novel disease modulator for human asthmatics/allergic diseases. This article is protected by copyright. All rights reserved.
 

Allergy. 2015 May 13. doi: 10.1111/all.12651. [Epub ahead of print]