The antimicrobial/elastase inhibitor elafin regulates lung dendritic cells and adaptive immunity
The antimicrobial/elastase inhibitor elafin regulates lung dendritic cells and adaptive immunity
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DOI：
10.1165/rcmb.2005-0405oc
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发表时间：
2006-05-01
影响因子：
6.4
通讯作者：
Sallenave, JM
中科院分区：
文献类型：
--
作者：
Roghanian, A;Williams, SE;Sallenave, JM
细菌和病毒（如腺病毒）感染是慢性肺部疾病（如慢性阻塞性肺疾病（COPD））的一个特征，可能有助于疾病恶化的产生。我们之前在急性模型中表明，elafin（巨噬细胞和中性粒细胞的天然趋化分子，具有有效的抗菌和中性粒细胞弹性酶抑制剂活性）在感染中上调并调节先天免疫。在这里，我们使用两个独立的体内过表达系统（重组腺病毒[Ad-elafin]和elafin转基因小鼠系）来研究elafin在适应性免疫中的功能。我们发现elafin增加了体内CD11c(+)/MHCII+肺树突状细胞的数量（免疫荧光）和激活状态（流式细胞术测量）。脾和肺细胞产生的细胞因子分析以及血清和支气管肺泡灌洗液中测量的抗体显示，诱导的免疫倾向于1型应答（产生IL-12、ifn - γ和IgG2a）。此外，通过抗体水平和中和滴度以及肺组织中LacZ的表达来评估，elafin过表达可以保护小鼠免受Ad-LacZ的进一步攻击。因此，多效性分子elafin在调节抗原呈递细胞数量和活性方面具有显著的潜力，并可能在粘膜保护策略中有益。
Infections with bacteria and viruses such as adenovirus are a feature of chronic lung diseases such as chronic obstructive pulmonary diseases (COPD), and may be instrumental in the generation of disease exacerbations. We have previously shown in acute models that elafin (a lung natural chemotactic molecule for macrophages and neutrophils, with potent antimicrobial and neutrophil elastase inhibitor activity) is upregulated in infection and modulates innate immunity. Here we present data using two independent systems of elafin overexpression in vivo (recombinant adenovirus [Ad-elafin] and an elafin transgenic mouse line) to examine the function of elafin in adaptive immunity. We show that elafin increases the number (immunofluorescence) and activation status (flow cytometric measurement) of CD11c(+)/MHCII+ lung dendritic cells in vivo. Analysis of cytokines produced by spleen and lung cells, and of antibodies measured in serum and bronchoalveolar lavage fluid, shows that the immunity induced is biased toward a type 1 response (production of IL-12, IFN-gamma, and IgG2a). Furthermore, elafin overexpression protected mice against further challenge with Ad-LacZ, as assessed by antibody levels and neutralization titer, as well as LacZ expression in lung tissue. Thus, the pleiotropic molecule elafin has significant potential in modulating antigen-presenting cell numbers and activity, and could be beneficial in mucosal protective strategies.