Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation
Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation
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DOI：
10.1183/09031936.05.00091804
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发表时间：
2005-03-01
影响因子：
24.3
通讯作者：
Bewig, B
中科院分区：
文献类型：
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作者：
Hübner, RH;Meffert, S;Bewig, B
闭塞性细支气管炎综合征（BOS）是肺移植（LTX）后的严重并发症，本研究对12例稳定的健康受者（非BOS）和8例BOS患者行LTX后的支气管肺泡灌洗液（BAL）标本（n=145）进行了基质金属蛋白酶（MMP）-9、金属蛋白酶组织抑制剂（TIMP）-1和细胞学特征分析。BOS患者巴尔斯中MMP-9/TIMP-1比值与1秒用力呼气量呈负相关，与非BOS和BOS前比较差异有统计学意义（P < 0. 05）。在酶谱分析中，MMP-9的活性形式主要在BOS组中检测到。此外，酶谱显示嗜中性粒细胞衍生的MMP-9的带型，表明多形核中性粒细胞（PMNs）是MMP-9的主要来源。MMP 9与PMN数量呈显著正相关。在免疫细胞化学中，MMP-9也主要与PMN相关。这是第一项研究，以评估随着时间的推移，在纤维增生性肺疾病的患者表现的基质金属蛋白酶-9和金属蛋白酶-1的组织抑制剂的表达。这表明肺移植后闭塞性细支气管炎综合征的发生与基质金属蛋白酶-9/金属蛋白酶组织抑制剂-1比例失衡有关。
Bronchiolitis obliterans syndrome (BOS) is a severe complication after lung transplantation (LTX).In a retrospective cohort study 12 stable healthy recipients (non-BOS) and eight patients with BOS were enrolled after LTX and matrix metalloproteinases (MMP)-9, TIMP-1 and cell characteristics in bronchoalveolar lavage (BAL) samples (n=145) were analysed. BALs from patients with BOS were further divided according to whether they were obtained before (pre-BOS) or after manifestation of BOS (BOS group).The MMP-9/TIMP-1 ratio was significantly increased in the BOS group compared with non-BOS or pre-BOS; furthermore, the ratio was negatively correlated with forced expiratory volume in one second. In zymography, the active form of MMP-9 was detected predominantly in the BOS group. In addition, zymography showed the banding pattern of neutrophil-derived MMP-9, indicating that polymorphonuclear neutrophils (PMNs) were the main source of MMP-9. According to that, MMP9 was significantly correlated with the number of PMN. In immunocytochemistry, MMP-9 was also associated predominantly with PMN.This is the first study to evaluate the expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 over time during manifestation of a fibroproliferative lung disease in patients. It demonstrates development of bronchiolitis obliterans syndrome after lung transplantation is associated with an imbalance of matrix metalloproteinases-9/tissue inhibitors of metalloproteinase-1 ratio.