Lung transplant metalloproteinase levels are elevated prior to bronchiolitis obliterans syndrome
Lung transplant metalloproteinase levels are elevated prior to bronchiolitis obliterans syndrome
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DOI：
10.1111/j.1600-6143.2007.01850.x
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发表时间：
2007-07-01
影响因子：
8.8
通讯作者：
Wilkes, D. S.
中科院分区：
文献类型：
--
作者：
Smith, G. N., Jr.;Mickler, E. A.;Wilkes, D. S.
同种异体移植肺的实质疾病与间质重塑有关，据信这是由基质金属蛋白酶（MMP）介导的。最近的研究表明，肺移植受者中高水平的 MMP-9 与闭塞性细支气管炎综合征 (BOS) 相关。由于 BOS 发生在移植后后期，并且之前可能发生与间质重塑相关的急性排斥或感染，因此我们检查了移植后早期（BOS 之前）同种异体移植物支气管肺泡灌洗 (BAL) 液中的 MMP 谱。对移植肺 BAL 液的明胶酶谱分析、蛋白芯片分析和特异性 ELISA 表明，与正常志愿者的 BAL 液相比，稳定患者或感染或排斥反应患者的同种异体移植 BAL 液中 MMP-8、MMP-9 和 TIMP-1 强烈表达。 MMP-8、MMP-9 和 TIMP-1 的表达升高发生得很早，并持续了本研究涵盖的 3.2 年。移植后头 2 年 MMP-8、MMP-9 和 TIMP-1 的升高似乎与肺移植本身有关，而不是感染或排斥。这些数据表明，持续且临床上沉默的 MMP 活性可能会使同种异体移植肺中的进展性疾病永久存在。
Parenchymal disease in the allograft lung is associated with interstitial remodeling believed to be mediated by matrix metalloproteinases (MMPs). Recent studies suggest high levels of MMP-9 are associated with bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Since BOS occurs late in the posttransplant period and may be preceded by episodes of acute rejection or infection, which are associated with interstitial remodeling, we examined MMP profiles in allograft bronchoalveolar lavage (BAL) fluid in the early posttransplant period (preceding BOS). Gelatin zymography, protein array analysis and specific ELISA on BAL fluids from transplanted lungs indicated that MMP-8, MMP-9 and TIMP-1 were strongly expressed in allograft BAL fluid from stable patients, or those with infection or rejection compared to BAL fluid from normal volunteers. Elevated expression of MMP-8, MMP-9 and TIMP-1 occurred early, and was sustained for the 3.2 years covered in this study. Elevations of MMP-8, MMP-9 and TIMP-1 in the first 2 years posttransplant appear to be associated with lung transplantation itself, and not infection or rejection. These data suggest that ongoing and clinically silent MMP activity could perpetuate progressive disease in the allograft lung.