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首页> 外文期刊>Allergy >Systemic FasL neutralization increases eosinophilic inflammation in a mouse model of asthma
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Systemic FasL neutralization increases eosinophilic inflammation in a mouse model of asthma

机译：系统性FasL中和作用会增加哮喘小鼠的嗜酸性粒细胞炎症

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Background: Eosinophils and lymphocytes are pathogenically important in allergic inflammation and sensitive to Fas-mediated apoptosis. Fas ligand (FasL) activity therefore should play a role in regulating the allergic immune response. We aimed to characterize the role of FasL expression in airway eosinophilia in Aspergillus fumigatus (Af)-induced sensitization and to determine whether FasL neutralization alters the inflammatory response. Methods: Sensitized Balb/c mice were killed before (day 0) and 1, 7 and 10 days after a single intranasal challenge with Af. Animals received either neutralizing antibody to FasL (clone MFL4) or irrelevant hamster IgG via intraperitoneal injection on days -1 and 5. FasL expression, BAL and tissue inflammatory cell and cytokine profile, and apoptosis were assessed. Results: Postchallenge FasL gene expression in BAL cells and TUNEL positivity in the airways coincided with the height of inflammatory cell influx on day 1, while soluble FasL protein was released on day 7, preceding resolution of the inflammatory changes. Although eosinophil numbers showed a negative correlation with soluble FasL levels in the airways, MBP + eosinophils remained TUNEL negative in the submucosal tissue, throughout the 10-day period after Af challenge. Systemic FasL neutralization significantly enhanced BAL and tissue eosinophil counts. This effect was associated with increased activation of T cells and release of IL-5, IL-9, and GM-CSF in the BAL fluid of mice, indicating an involvement of pro-eosinophilic survival pathways. Conclusions: FasL activity may play an active role in resolving eosinophilic inflammation through regulating T cells and pro-eosinophilic cytokine release during the allergic airway response.
机译：背景：嗜酸性粒细胞和淋巴细胞在变态反应性炎症中具有重要的致病性，并且对Fas介导的细胞凋亡敏感。因此，FasL（FasL）活性应在调节过敏性免疫应答中发挥作用。我们旨在表征FasL表达在烟曲霉（Af）致敏的气道嗜酸性粒细胞增多中的作用，并确定FasL中和是否改变炎症反应。方法：敏化的Balb / c小鼠在一次鼻内用Af攻击之前（第0天），1、7和10天被杀死。在第-1天和第5天，通过腹膜内注射动物接受FasL（克隆MFL4）的中和抗体或无关的仓鼠IgG。评估了FasL的表达，BAL，组织炎性细胞和细胞因子的分布以及凋亡。结果：攻击后第1天，BAL细胞中FasL基因表达和气道TUNEL阳性与炎性细胞流入高度一致，而可溶性FasL蛋白在第7天被释放，从而消除了炎症变化。尽管嗜酸性粒细胞数量与呼吸道中的可溶性FasL水平呈负相关，但在Af攻击后的10天内，MBP +嗜酸性粒细胞在粘膜下组织中仍保持TUNEL阴性。全身FasL中和作用可显着提高BAL和组织嗜酸性粒细胞计数。这种作用与小鼠BAL液中T细胞活化的增强和IL-5，IL-9和GM-CSF的释放有关，表明嗜酸性粒细胞的生存途径参与其中。结论：FasL活性可能通过在过敏性气道反应过程中调节T细胞和促嗜酸性细胞因子的释放来解决嗜酸性炎症。

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