Procollagen III N-terminal Propeptide and Desmosine are Released by Matrix Destruction in Pulmonary Tuberculosis

Background. Tuberculosis is transmitted by patients with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in tuberculosis but the resulting matrix degradation products (MDPs) have not been studied. We investigate the hypothesis that MMP activity generates matrix turnover pr...

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Bibliographic Details
Published in:The Journal of infectious diseases 2013-11, Vol.208 (10), p.1571-1579
Main Authors: Seddon, Jo, Kasprowicz, Victoria, Walker, Naomi F., Yuen, Ho Ming, Sunpath, Henry, Tezera, Liku, Meintjes, Graeme, Wilkinson, Robert J., Bishai, William R., Friedland, Jon S., Elkington, Paul T.
Format: Article
Language:English
Subjects:
BACTERIA
Bacterial diseases
Bacterial diseases of the respiratory system
Biological and medical sciences
Biomarkers
Blood plasma
Coinfection
Collagens
Cytokines
Desmosine - metabolism
Extracellular Matrix - metabolism
Extracellular Matrix - pathology
Fundamental and applied biological sciences. Psychology
HIV
HIV Seropositivity
Human bacterial diseases
Infectious diseases
Lungs
Major and Brief Reports
Matrix Metalloproteinases - blood
Matrix Metalloproteinases - metabolism
Medical sciences
Microbiology
Mycobacterium tuberculosis
Pathology
Peptide Fragments - blood
Peptide Fragments - metabolism
Procollagen - blood
Procollagen - metabolism
Pulmonary tuberculosis
Reproducibility of Results
ROC Curve
Sputum
Sputum - chemistry
Tuberculosis
Tuberculosis, Pulmonary - metabolism
Tuberculosis, Pulmonary - pathology
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Summary:Background. Tuberculosis is transmitted by patients with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in tuberculosis but the resulting matrix degradation products (MDPs) have not been studied. We investigate the hypothesis that MMP activity generates matrix turnover products as correlates of lung pathology. Methods. Induced sputum and plasma were collected prospectively from human immunodeficiency virus (HIV) positive and negative patients with pulmonary tuberculosis and controls. Concentrations of MDPs and MMPs were analyzed by ELISA and Luminex array in 2 patient cohorts. Results. Procollagen III N-terminal propeptide (PIIINP) was 3.8-fold higher in induced sputum of HIVuninfected tuberculosis patients compared to controls and desmosine, released during elastin degradation, was 2.4-fold higher. PIIINP was elevated in plasma of tuberculosis patients. Plasma PIIINP correlated with induced sputum MMP-1 concentrations and radiological scores, demonstrating that circulating MDPs reflect lung destruction. In a second patient cohort of mixed HIV seroprevalence, plasma PIIINP concentration was increased 3.0-fold above controls (P
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jit343