Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

BMC Pulmonary Medicine

Morten A Karsdal²  Diana J Leeming²  Arkadiusz Nawrocki¹  Martin R Larsen¹  Lloyd B Klickstein⁴  Meilan Han³  Cory M Hogaboam³  Fernando J Martinez³  Qinlong Zheng⁶  Yaguo Wang⁶  Quoc Hai Trieu Nguyen²  Rikke E Clausen²  Helene Skjøt-Arkil⁵ 

[1] Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark;Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730, Herlev, Denmark;Division of Pulmonary and Critical Care Medicine and Department of Pathology, University of Michigan, Ann Arbor, MI, USA;Novartis Institutes for Biomedical Research, Cambridge, MA, USA;Institute of Clinical Research, Odense University Hospital, Odense, Denmark;Nordic Bioscience Beijing, Beijing, China

关键词: MMP;    IPF;    COPD;    Neoepitope;    Biochemical marker;    Extracellular matrix remodeling;    Elastin;   

Others  :  1161085
DOI  :  10.1186/1471-2466-12-34

 received in 2012-01-03, accepted in 2012-07-03,  发布年份 2012

【 摘 要 】

Background

Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases.

Methods

Elastin fragments were identified by mass-spectrometry and one sequence, generated by MMP-9 and -12 (ELN-441), was selected for monoclonal antibody generation and used in the development of an ELISA. Soluble and insoluble elastin from lung was cleaved in vitro and the time-dependent release of fragments was assessed in the ELN-441 assay. The release of ELN-441 in human serum from patients with chronic obstructive pulmonary disease (COPD) (n = 10) and idiopathic pulmonary fibrosis (IPF) (n = 29) were compared to healthy matched controls (n = 11).

Results

The sequence ELN-441 was exclusively generated by MMP-9 and -12 and was time-dependently released from soluble lung elastin. ELN-441 levels were 287% higher in patients diagnosed with COPD (p < 0.001) and 124% higher in IPF patients (p < 0.0001) compared with controls. ELN-441 had better diagnostic value in COPD patients (AUC 97%, p = 0.001) than in IPF patients (AUC 90%, p = 0.0001). The odds ratios for differentiating controls from COPD or IPF were 24 [2.06–280] for COPD and 50 [2.64–934] for IPF.

Conclusions

MMP-9 and -12 time-dependently released the ELN-441 epitope from elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in larger clinical settings.

【 授权许可】

   
2012 Skjøt-Arkil et al.; licensee BioMed Central Ltd.

【 图 表 】

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