Procollagen III N-terminal propeptide and desmosine are released by matrix destruction in pulmonary tuberculosis
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 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 HIV-uninfected 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 < .001). Plasma matrix metalloproteinase-8 concentrations were also higher in tuberculosis patients (P = .001). Receiver operating characteristic analysis utilizing these 2 variables demonstrated an area under the curve of 0.832 (P < .001).
CONCLUSIONS: In pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products.
lung, mycobacteria, immunopathology, extracellular matrix, matrix metalloproteinase
1571-1579
Seddon, Jo
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Kasprowicz, Victoria
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Walker, Naomi F.
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Yuen, Ho Ming
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Sunpath, Henry
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Tezera, Liku
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Meintjes, Graeme
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Wilkinson, Robert J.
efcf7079-ebfa-4270-b7a4-a578ffd91178
Bishai, William R.
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Friedland, Jon S.
9968669f-afe0-4163-9b35-3b476246fd4a
Elkington, Paul T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
November 2013
Seddon, Jo
cd1cc26c-f44f-4530-9cee-632f4cc93424
Kasprowicz, Victoria
28cebde0-dda6-4433-ba45-c3039b1223a7
Walker, Naomi F.
e586ffdf-ae4b-46fa-83a1-db72501d17c1
Yuen, Ho Ming
b1df4c57-0c2a-44ac-ab40-22b88e8effe8
Sunpath, Henry
f72d9cbf-7fdd-43e0-89b0-badede9fcb5c
Tezera, Liku
c5598dbf-23a8-4934-96a4-7c783bf9e776
Meintjes, Graeme
6ba420af-cfb0-412b-b4a4-2749517cd0a2
Wilkinson, Robert J.
efcf7079-ebfa-4270-b7a4-a578ffd91178
Bishai, William R.
d12021cd-50f9-4ac7-b89b-ecb8a73f735b
Friedland, Jon S.
9968669f-afe0-4163-9b35-3b476246fd4a
Elkington, Paul T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
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. and Elkington, Paul T.
(2013)
Procollagen III N-terminal propeptide and desmosine are released by matrix destruction in pulmonary tuberculosis.
The Journal of Infectious Diseases, 208 (10), .
(doi:10.1093/infdis/jit343).
(PMID:23922364)
Abstract
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 HIV-uninfected 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 < .001). Plasma matrix metalloproteinase-8 concentrations were also higher in tuberculosis patients (P = .001). Receiver operating characteristic analysis utilizing these 2 variables demonstrated an area under the curve of 0.832 (P < .001).
CONCLUSIONS: In pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products.
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e-pub ahead of print date: 6 August 2013
Published date: November 2013
Keywords:
lung, mycobacteria, immunopathology, extracellular matrix, matrix metalloproteinase
Organisations:
Primary Care & Population Sciences, Clinical & Experimental Sciences
Identifiers
Local EPrints ID: 355591
URI: http://eprints.soton.ac.uk/id/eprint/355591
ISSN: 0022-1899
PURE UUID: eb1dfc2e-f8f5-4b58-9ca0-8fe3bcc7e042
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Date deposited: 02 Sep 2013 15:40
Last modified: 15 Mar 2024 03:45
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Contributors
Author:
Jo Seddon
Author:
Victoria Kasprowicz
Author:
Naomi F. Walker
Author:
Henry Sunpath
Author:
Graeme Meintjes
Author:
Robert J. Wilkinson
Author:
William R. Bishai
Author:
Jon S. Friedland
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