Chemokine expression in Th1 cell-induced lung injury:: prominence of IFN-γ-inducible chemokines
Chemokine expression in Th1 cell-induced lung injury:: prominence of IFN-γ-inducible chemokines
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DOI：
10.1152/ajplung.2000.279.3.l592
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发表时间：
2000-09-01
影响因子：
4.9
通讯作者：
Clark, JG
中科院分区：
文献类型：
--
作者：
Dixon, AE;Mandac, JB;Clark, JG
1 型辅助 T (Th1) 细胞产生的促炎反应可能对免疫介导的肺损伤有显着影响。我们描述了 Th1 细胞诱导的肺损伤的小鼠模型，其中同种异体反应性 Th1 细胞的过继转移产生以单核细胞血管炎、肺泡炎和间质性肺炎为特征的肺部炎症。为了研究肺中 Th1 细胞的激活与炎症细胞募集之间的联系，我们对体外激活的 Th1 细胞以及 Th1 细胞过继转移后肺组织中的细胞因子和趋化因子 mRNA 表达进行了表征。活化的 Th1 细胞本身表达干扰素 (IFN)-γ 和肿瘤坏死因子家族的几个成员的 mRNA，以及调节正常 T 细胞表达和分泌的活化的 C-C 趋化因子受体 5 配体以及巨噬细胞炎症蛋白 1 α 和 -1 β。给予 Th1 细胞后，肺中诱导了其他趋化因子基因，最显着的是 IFN-γ 诱导蛋白 (IP-10) 和 IFN-γ 诱导的单因子 (MIG)。肺部炎症病灶中 IP-10 和 MIG 免疫反应蛋白显着增加，并在巨噬细胞、内皮、支气管上皮和肺泡结构中得到鉴定。研究结果表明，IFN-γ诱导的趋化因子是放大肺部 Th1 细胞引发的炎症的重要机制。
Proinflammatory responses generated by T helper type 1 (Th1) cells may contribute significantly to immune-mediated lung injury. We describe a murine model of Th1 cell-induced lung injury in which adoptive transfer of alloreactive Th1 cells produces pulmonary inflammation characterized by mononuclear cell vasculitis, alveolitis, and interstitial pneumonitis. To investigate the link between activation of Th1 cells in the lung and inflammatory cell recruitment, we characterized cytokine and chemokine mRNA expression in Th1 cells activated in vitro and in lung tissue after adoptive transfer of Th1 cells. Activated Th1 cells per se express mRNA for interferon (IFN)-gamma and several members of the tumor necrosis factor family as well as the C-C chemokine receptor-5 ligands regulated on activation normal T cells expressed and secreted and macrophage inflammatory protein-1 alpha and -1 beta. Additional chemokine genes were induced in the lung after Th1 cell administration, most notably IFN-gamma-inducible protein (IP-10) and monokine induced by IFN-gamma (MIG). Remarkable increases in IP-10- and MIG-immunoreactive proteins were present in inflammatory foci lung and identified in macrophages, endothelium, bronchial epithelium, and alveolar structures. The findings suggest that IFN-gamma-inducible chemokines are an important mechanism for amplifying inflammation initiated by Th1 cells in the lung.