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N-α-PGP and PGP, potential biomarkers and therapeutic targets for COPD
- Source :
- Respiratory Research, Vol 10, Iss 1, p 38 (2009), Respiratory Research
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
Abstract
- Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder for which new diagnostic and therapeutic approaches are required. Hallmarks of COPD are matrix destruction and neutrophilic airway inflammation in the lung. We have previously described two tri-peptides, N-α-PGP and PGP, which are collagen fragments and neutrophil chemoattractants. In this study, we investigate if N-α-PGP and PGP are biomarkers and potential therapeutic targets for COPD. Methods Induced sputum samples from COPD patients, healthy controls and asthmatics were examined for levels of N-α-PGP and PGP using mass spectrometry and for the ability to generate PGP de novo from collagen. Proteases important in PGP generation in the lung were identified by the use of specific inhibitors in the PGP generation assay and by instillation of proteases into mouse lungs. Serum levels of PGP were compared between COPD patients and controls. Results N-α-PGP was detected in most COPD sputum samples but in no asthmatics or controls. PGP was detected in a few controls and in all COPD sputum samples, where it correlated with levels of myeloperoxidase. COPD sputum samples had the ability to generate N-α-PGP and PGP de novo from collagen. PGP generation by COPD sputum was blocked by inhibitors of matrix metalloproteases (MMP's) 1 and 9 and prolyl endopeptidase. MMP's 1 and 9 and prolyl endopeptidase acted synergistically to generate PGP in vivo when instilled into mouse lungs. Serum levels of PGP were also significantly higher in COPD patients than in controls Conclusion N-α-PGP and PGP may represent novel diagnostic tests and biomarkers for COPD. Inhibition of this pathway may provide novel therapies for COPD directed at the chronic, neutrophilic, airway inflammation which underlies disease progression.
- Subjects :
- endocrine system diseases
Vital Capacity
Matrix metalloproteinase
Mice
Pulmonary Disease, Chronic Obstructive
0302 clinical medicine
Reference Values
Forced Expiratory Volume
polycyclic compounds
Medicine
0303 health sciences
COPD
integumentary system
biology
3. Good health
medicine.anatomical_structure
Matrix Metalloproteinase 9
Myeloperoxidase
Collagen
Matrix Metalloproteinase 1
medicine.symptom
Oligopeptides
medicine.drug
Pulmonary and Respiratory Medicine
Spectrometry, Mass, Electrospray Ionization
Proteases
03 medical and health sciences
Prolyl endopeptidase
Animals
Humans
Protease Inhibitors
Peroxidase
030304 developmental biology
Asthma
lcsh:RC705-779
Lung
business.industry
Research
Sputum
lcsh:Diseases of the respiratory system
medicine.disease
respiratory tract diseases
carbohydrates (lipids)
030228 respiratory system
Immunology
biology.protein
business
Biomarkers
Subjects
Details
- ISSN :
- 1465993X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Respiratory Research
- Accession number :
- edsair.doi.dedup.....e5a0c40e5e085fc9b8883186ac1bd072