Regulation of pulmonary inflammation and fibrosis through expression of integrins alphaVbeta3 and alphaVbeta5 on pulmonary T lymphocytes.
Regulation of pulmonary inflammation and fibrosis through expression of integrins alphaVbeta3 and alphaVbeta5 on pulmonary T lymphocytes.
复制标题
DOI：
10.1002/art.24435
复制
发表时间：
2009-05
影响因子：
--
通讯作者：
Atamas, Sergei P.
中科院分区：
文献类型：
--
作者：
Luzina, Irina G.;Todd, Nevins W.;Nacu, Natalia;Lockatell, Virginia;Choi, Jung;Hummers, Laura K.;Atamas, Sergei P.
与纤维化相关的肺部疾病，包括硬皮病肺部疾病，其特征是T细胞在肺内积聚。这些细胞被认为促进了肺纤维化，但其促纤维化作用的确切机制尚不清楚。一些含有αV的整合素，包括αVβ3和αVβ5，已经被证明可以直接激活转化生长因子-β，促进胶原的积累。肺T细胞是否表达促纤维化整合素并调节胶原堆积尚不清楚。用免疫组织化学和流式细胞术检测肺组织中整合素的表达，从患者或CCL18高表达的肺T细胞浸润动物模型中检测肺泡灌洗液(BAL)中整合素的表达。细胞培养实验测试了表达整合素的T细胞在与肺成纤维细胞共培养时是否具有促纤维化作用，以及可能的机制。在患者和动物模型中，肺内存在淋巴细胞和整合素阳性细胞，肺T细胞表达整合素αVβ3和αVβ5。全身应用中和抗整合素αV抗体或CCL18过表达模型中整合素β3的遗传缺陷可显著减轻CCL18诱导的肺淋巴细胞浸润和胶原沉积。在与原代肺成纤维细胞共培养时，Jurkat T细胞过表达整合素αVβ3或整合素αVβ5，可刺激胶原堆积和Smad2核转位。中和抗转化生长因子-β抗体可减弱表达整合素的T细胞的促纤维化作用。肺浸润性T淋巴细胞可表达整合素αVβ3和αVβ5，它们是淋巴细胞浸润、T细胞相关的转化生长因子β活化和胶原沉积所必需的。
Pulmonary diseases associated with fibrosis, including scleroderma lung disease, are characterized by accumulation of T cells in the lungs. These cells are thought to facilitate lung fibrosis, but the exact mechanisms of their profibrotic action are not clear. Several αV-containing integrins, including αVβ3 and αVβ5 have been shown to directly activate TGF-β and promote collagen accumulation. Whether pulmonary T cells express profibrotic integrins and regulate collagen accumulation is unknown. Expression of integrins was assessed by immunohistochemistry in the lung tissue and by flow cytometry in bronchoalveolar lavage (BAL) from patients or from a CCL18 overexpression animal model of pulmonary T cell infiltration. Experiments in cell culture tested whether integrin-expressing T cells are profibrotic in co-cultures with pulmonary fibroblasts and through what possible mechanism. Lymphocytes and integrin-positive cells were present in the lungs, and pulmonary T cells expressed integrins αVβ3 and αVβ5, in patients and in the animal model. Systemic administration of neutralizing anti-integrin αV antibody or genetic deficiency of integrin β3 in the CCL18 overexpression model significantly attenuated CCL18-driven pulmonary lymphocytic infiltration and collagen accumulation. Jurkat T cells overexpressing integrin αVβ3 or integrin αVβ5 in co-cultures with primary pulmonary fibroblasts stimulated collagen accumulation and Smad2 nuclear translocation. Neutralizing anti-TGF-β antibody attenuated the profibrotic effect of integrin-expressing T cells. Pulmonary infiltrating T lymphocytes may express integrins αVβ3 and αVβ5 that are necessary for lymphocytic infiltration and T cell-associated TGF-β activation and collagen accumulation.
登录
查看更多内容
影响因子：
5.3
作者：
Wicks, SJ;Lui, S;Chantry, A
通讯作者：
Chantry, A
DOI：
10.1165/rcmb.2003-0078oc
发表时间：
2003-12-01
影响因子：
6.4
作者：
Atamas, SP;Luzina, IG;White, B
通讯作者：
White, B
影响因子：
--
作者：
Luzina, IG;Atamas, SP;White, B
通讯作者：
White, B
影响因子：
6.5
作者：
Asano, Yoshihide;Ihn, Hironobu;Tamaki, Kunihiko
通讯作者：
Tamaki, Kunihiko
影响因子：
4.4
作者：
Atamas, SP;Luzina, IG;White, B
通讯作者：
White, B