The perforin mediated apoptotic pathway in lung injury and fibrosis
The perforin mediated apoptotic pathway in lung injury and fibrosis
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DOI：
10.1136/jcp.2003.015495
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发表时间：
2004-12-01
影响因子：
3.4
通讯作者：
Nakanishi, Y
中科院分区：
文献类型：
--
作者：
Miyazaki, H;Kuwano, K;Nakanishi, Y
目的：穿孔素介导的细胞毒途径是活化T细胞和自然杀伤细胞介导的细胞毒作用的主要途径，可能参与肺纤维化的发生发展。采用免疫组织化学方法检测特发性肺纤维化中穿孔素和颗粒酶B的表达，和穿孔素基因敲除小鼠用于检查穿孔素介导的细胞毒性是否参与博来霉素诱导的细胞凋亡的病理生理学。结果：与正常肺实质相比，特发性肺纤维化患者肺组织浸润淋巴细胞中穿孔素和颗粒酶B表达上调。在野生型小鼠中，博来霉素滴注后，穿孔蛋白和颗粒酶B表达主要在浸润的单核细胞中上调。虽然博莱霉素引起的肺病的发展并没有完全阻止，炎症和纤维化的病理分级，肺组织中的凋亡细胞的数量，穿孔素基因敲除小鼠相比，野生型mice.Conclusions：这些结果表明，穿孔素介导的细胞凋亡可能与肺损伤和纤维化的病理生理学。
Aims: The perforin mediated pathway is the major pathway of cytotoxicity induced by activated T cells and natural killer cells, and may be involved in the development of pulmonary fibrosis.Methods: Perforin and granzyme B expression were examined in idiopathic pulmonary fibrosis by means of immunohistochemistry, and perforin knockout mice were used to examine whether or not perforin mediated cytotoxicity participates in the pathophysiology of bleomycin induced pneumopathy.Results: Perforin and granzyme B expression were upregulated in infiltrating lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis compared with normal lung parenchyma. Perforin and granzyme B expression were upregulated predominantly in infiltrating mononuclear cells after bleomycin instillation in wild-type mice. Although the development of bleomycin induced pneumopathy was not completely prevented, the pathological grade of inflammation and fibrosis, and the number of apoptotic cells in lung tissue, were significantly decreased in perforin knockout mice compared with wild-type mice.Conclusions: These results suggest that perforin mediated apoptosis may be associated with the pathophysiology of lung injury and fibrosis.