A Gaggar

AE Postlethwaite

AH van Houwelingen

AM Houghton

AV Bakker

B Suki

CJ Murray

D Stanescu

DL Laskin

GA Finlay

I Stamenkovic

J Pugin

JI Levin

JL Haddox

K Imai

K Kawabata

KD Kochanek

KM Beeh

M Cazzola

M Ikejiri

M Lin

M Ogawa

National Heart, Lung and Blood Institute and World Health Organization

NM Siafakas

NM Weathington

PJ O'Reilly

PL Paggiaro

RD Hautamaki

RF Foronjy

RM Senior

RR Pfister

SD Shapiro

SM Rowe

SV Culpitt

TL Croxton

WC Moore

YS Lopez-Boado

English

PubMed

Crossref

N-α-PGP and PGP, potential biomarkers and therapeutic targets for COPD

Philip O'Reilly

Patricia L Jackson

Brett Noerager

Suzanne Parker

Mark Dransfield

Amit Gaggar

J Edwin Blalock

Springer - Publisher Connector

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.</p

Gaggar Amit

Dransfield Mark

Parker Suzanne

Noerager Brett

Jackson Patricia L

O'Reilly Philip

Blalock J Edwin

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N-α-PGP and PGP, potential biomarkers and therapeutic targets for COPD

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Springer - Publisher Connector

Directory of Open Access Journals

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