Hübner R H, Meffert S, Mundt U, Böttcher H, Freitag S, El Mokhtari N E, Pufe T, Hirt S, Fölsch U R, Bewig B
Dept of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr.12, 24105 Kiel, Germany.
Eur Respir J. 2005 Mar;25(3):494-501. doi: 10.1183/09031936.05.00091804.
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, MMP-9 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.
闭塞性细支气管炎综合征（BOS）是肺移植（LTX）后的一种严重并发症。在一项回顾性队列研究中，12名稳定健康的受者（非BOS）和8名BOS患者在肺移植后入组，并对支气管肺泡灌洗（BAL）样本（n = 145）中的基质金属蛋白酶（MMP）-9、基质金属蛋白酶组织抑制剂-1（TIMP-1）和细胞特征进行了分析。BOS患者的BAL样本根据是否在BOS表现之前（BOS前）或之后获得进一步分组（BOS组）。与非BOS或BOS前相比，BOS组的MMP-9/TIMP-1比值显著升高；此外，该比值与一秒用力呼气量呈负相关。在酶谱分析中，主要在BOS组中检测到MMP-9的活性形式。此外，酶谱分析显示了中性粒细胞来源的MMP-9的条带模式，表明多形核中性粒细胞（PMN）是MMP-9的主要来源。据此，MMP-9与PMN数量显著相关。在免疫细胞化学中，MMP-9也主要与PMN相关。这是第一项评估患者在纤维增生性肺病表现过程中随时间变化的基质金属蛋白酶-9和基质金属蛋白酶组织抑制剂-1表达的研究。它表明肺移植后闭塞性细支气管炎综合征的发展与基质金属蛋白酶-9/基质金属蛋白酶组织抑制剂-1比值失衡有关。
