Abstract | BACKGROUND: METHODS: We studied total MMP-1,-2,-3,-7,-8,-9,-12,-13 levels, their activity state using activity-based extraction and their binding to TIMP-1, -2, -3, and -4 in bronchoalveolar lavage (BAL) of lung transplant recipients with good outcome and BOS using a multiplex immunoassay. RESULTS: The BAL levels of TIMP-1 and -2 and MMP-2, -3, -7, -8, and -9 were significantly increased in BOS compared to good outcome recipients. Interestingly, activity of MMP-7, but none of the other MMPs, was detected in good outcome recipients, whereas no active MMPs were observed in BOS recipients. However, BAL levels of TIMP-bound MMP-8 and -9 were higher in BOS than in good outcome recipients, suggesting activity of these MMPs in an earlier stage. CONCLUSIONS: We demonstrate that development of BOS is associated with increased levels of TIMP-1 and -2 and total MMP-2, -3, -7, -8, and -9. Although active MMP-7 was only observed in good outcome recipients, levels of TIMP-bound MMP-8 and -9 were higher in BOS. By enabling profiling of active and TIMP-bound MMPs, our novel method may open opportunities for the screening of early predictors for BOS.
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Authors | Irene H Heijink, Dennie Rozeveld, Sicco van der Heide, Wim van der Bij, Rainer Bischoff, Antoon J van Oosterhout, Marco van der Toorn |
Journal | Transplantation
(Transplantation)
Vol. 99
Issue 9
Pg. 1946-52
(Sep 2015)
ISSN: 1534-6080 [Electronic] United States |
PMID | 25651312
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Tissue Inhibitor of Metalloproteinases
- Matrix Metalloproteinases
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Topics |
- Adult
- Biomarkers
(analysis)
- Bronchiolitis Obliterans
(diagnosis, enzymology, etiology)
- Bronchoalveolar Lavage Fluid
(chemistry)
- Female
- Humans
- Immunoassay
- Lung Transplantation
(adverse effects)
- Male
- Matrix Metalloproteinases
(analysis)
- Middle Aged
- Proteomics
(methods)
- Retrospective Studies
- Tissue Inhibitor of Metalloproteinases
(analysis)
- Treatment Outcome
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