title: Metalloproteinase Profiling in Lung Transplant Recipients With Good Outcome and Bronchiolitis Obliterans Syndrome.
abstract: BACKGROUND
  Bronchiolitis obliterans syndrome (BOS), the major cause of death on lung transplantation, is characterized by bronchiolar inflammation and tissue remodeling. Matrix metalloproteinases (MMPs) have been implicated in these processes, although it is still unclear whether MMP activity and binding to their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), is abnormal in BOS.
  
  
  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.
authors: 1 Department of Pathology and Medical Biology, Experimental Pulmonology and Inflammation Research, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. 2 Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. 3 GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 4 Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. 5 Department of Analytical Biochemistry, Center for Pharmacy, University of Groningen, the Netherlands.
authors: Irene H
authors: IH
authors: Heijink
authors: Dennie
authors: D
authors: Rozeveld
authors: Sicco
authors: S
authors: van der Heide
authors: Wim
authors: W
authors: van der Bij
authors: Rainer
authors: R
authors: Bischoff
authors: Antoon J
authors: AJ
authors: van Oosterhout
authors: Marco
authors: M
authors: van der Toorn
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001989:Bronchiolitis Obliterans / Q000175:diagnosis / Q000201:enzymology* / Q000209:etiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D007118:Immunoassay; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis*; D008875:Middle Aged; D040901:Proteomics / Q000379:methods; D012189:Retrospective Studies; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases