Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation.
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.
Hübner
R H
RH
Dept of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr.12, 24105 Kiel, Germany. rhuebner@1med.uni-kiel.de
Meffert
S
S
Mundt
U
U
Böttcher
H
H
Freitag
S
S
El Mokhtari
N E
NE
Pufe
T
T
Hirt
S
S
Fölsch
U R
UR
Bewig
B
B
D000328:Adult; D001989:Bronchiolitis Obliterans / Q000201:enzymology* / Q000209:etiology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D012016:Reference Values; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9