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1 Dept of Internal Medicine, and 2 Dept of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, 3 Institute for Medical Informatics and Statistics, and 4 Institute of Anatomy, Christian-Albrechts-University Kiel, and 5 Dept of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Germany
CORRESPONDENCE: R. H. Hübner, Dept of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr.12, 24105 Kiel, Germany. Fax: 49 4315971302. E-mail: rhuebner@1med.uni-kiel.de
Keywords: Bronchiolitis obliterans syndrome, bronchoalveloar lavage, lung transplantation, matrix metalloproteinase, polymorphonuclear cells, tissue inhibitors of matrix metalloproteinases
Received: August 3, 2004
Accepted November 24, 2004
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.
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