Granzyme K: a novel mediator in acute airway inflammation
Granzyme K: a novel mediator in acute airway inflammation
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DOI：
10.1136/thx.2007.091215
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发表时间：
2008-11-01
期刊：
影响因子：
10
通讯作者：
Virchow, J. C.
中科院分区：
文献类型：
--
作者：
Bratke, K.;Klug, A.;Virchow, J. C.
背景：颗粒酶是丝氨酸蛋白酶的一个亚家族，参与许多炎症性疾病的发病机制。与颗粒酶A和B相比，颗粒酶K（GrK）在人类肺部疾病中的作用尚不清楚。因此，释放和表达的GrK在过敏性哮喘，慢性阻塞性肺疾病（COPD）和bronchopropionies.Methods：可溶性GrK定量使用酶联免疫吸附试验在支气管肺泡灌洗液中的过敏性哮喘患者（节段性过敏原的挑战之前和之后），并在轻度COPD，肺炎和健康对照组的患者。通过western blot分析GrK的分子形式。结果：与健康对照组相比，过敏性哮喘患者和COPD患者支气管肺泡灌洗液中可溶性GrK水平正常。相反，急性支气管肺炎患者支气管肺泡灌洗液中的可溶性GrK强烈增加。在过敏性哮喘患者中，过敏原激发后24 h和72 h支气管肺泡灌洗液中可溶性GrK以及表达GrK的CD8（+）T细胞显著增加。过敏原刺激后，可溶性GrK与表达GrK的CD8（+）T细胞的百分比相关。最后，它表明，CCR5配体CCL3的支气管内释放可能是过敏原challenge.Conclusion后的GrK（+）CD8（+）T细胞的募集机制：这些数据提供了第一个证据，GrK的表达上调急性气道炎症，无论是在感染性和非感染性疾病。
Background: Granzymes are a subfamily of serine proteases involved in the pathogenesis of many inflammatory disorders. In contrast with granzyme A and B, the role of granzyme K (GrK) in human lung diseases is unknown. Therefore, the release and expression of GrK in allergic asthma, chronic obstructive pulmonary disease (COPD) and bronchopneumonia were investigated.Methods: Soluble GrK was quantified using an enzyme linked immunosorbent assay in the bronchoalveolar lavage fluid of patients with allergic asthma (before and after segmental allergen challenge), and in patients with mild COPD, pneumonia and in healthy controls. The molecular form of GrK was analysed by western blot. Flow cytometry was performed to determine the cellular expression of GrK.Results: Compared with healthy controls, there were normal levels of soluble GrK in the bronchoalveolar lavage fluid of patients with COPD, and patients with allergic asthma before allergen challenge. In contrast, soluble GrK was strongly increased in the bronchoalveolar lavage fluid of patients with acute bronchopneumonia. In patients with allergic asthma, there was a significant increase in soluble GrK as well as in GrK expressing CD8(+) T cells in the bronchoalveolar lavage fluid 24 h and 72 h after allergen challenge. After allergen challenge, soluble GrK correlated with the percentage of GrK expressing CD8(+) T cells. Finally, it was shown that the endobronchial release of the CCR5 ligand CCL3 might be a mechanism for the recruitment of GrK(+) CD8(+) T cells after allergen challenge.Conclusion: These data provide the first evidence that expression of GrK is upregulated in acute airway inflammation, both in infectious and non-infectious diseases.