2‐Chloroacetamidine, a novel immunomodulator, suppresses antigen‐induced mouse airway inflammation. Issue 9 (2nd June 2015)

• Record Type: Journal Article
• Authors: Maezawa, Y.; Paltser, G.; Tsui, H.; Cheung, R.; Wu, P.; Nicholas, A. P.; Dosch, H.‐M.
• Is Part Of: Allergy. Volume 70:Issue 9(2015:Sep.)
• Page Start: 1130
• Page End: 1138
• Publication Date: 2015-06-02
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12651
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" id="all12651-abs-0001"> <title>Abstract</title> <sec id="all12651-sec-0001" sec-type="section"> <title>Background</title> <p>Citrullination is a presently under‐recognized posttranslational 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.</p> </sec> <sec id="all12651-sec-0002" sec-type="section"> <title>Methods</title> <p>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 <italic>ex vivo</italic> lymphocytes and cell lines.</p> </sec> <sec id="all12651-sec-0003" sec-type="section"> <title>Results</title> <p> <italic>In vivo, </italic> 2CA dramatically suppressed lung tissue hypercitrullination, inflammatory cell recruitment, and airway‐Th2 cytokine secretion. 2CA also suppressed systemic OVA‐specific and total IgE production dramatically, effectively preventing <italic>de novo</italic> and diminishing established disease without measurably impacting general immunocompetence. <italic>In vitro</italic>, 2CA markedly inhibited the proliferation of mouse and human T cells with cell cycle block and apoptosis during a limited, postactivation phase.</p> </sec> <sec id="all12651-sec-0004" sec-type="section"> <title>Conclusions</title> <p>2CA acts as narrow‐spectrum immunosuppressant that selectively targets lymphocyte populations involved in active inflammatory tissue lesions. If hypercitrullination is generated in patients with asthma, 2CA may represent a novel disease modulator for human asthmatics/allergic diseases.</p> </sec> </abstract>