Med Central for supplementary material.AcknowledgmentsSupported by grants in the National Institutes of Wellness (RO1 AR057327, Dr. Costenbader); and the Canadian Institute of Health Study (Well being Experts Fellowship Award, Dr. Hiraki)
Key ARTICLEProcollagen III N-terminal Propeptide and Desmosine are Released by Matrix Destruction in Pulmonary TuberculosisJo Seddon,1,two,a Victoria Kasprowicz,3,4,a Naomi F. Walker,1,2,5,a Ho Ming Yuen,6 Henry Sunpath,7,8 Liku Tezera,9,10 Graeme Meintjes,5,11 Robert J. Wilkinson,5,11,12 William R. Bishai,3 Jon S. Friedland,1,two and Paul T. Elkington1,9,ten,Infectious Illnesses and Immunity, 2Wellcome Centre for Clinical Tropical Medicine, Imperial College London, London, Uk; 3Kwazulu-Natal Investigation Institute for Tuberculosis and HIV (K-RITH), Nelson Mandela School of Medicine, Durban, South Africa; 4Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Boston, Massachusetts; 5Clinical Infectious Diseases Investigation Initiative, Institute of Infectious Illness and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa; 6Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, United kingdom; 7McCord Hospital, Durban; 8Infectious Diseases Unit, Nelson Mandela College of Medicine, Durban; 9 Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, 10NIHR Respiratory Biomedical Analysis Unit, University Hospital Southampton, Southampton, Uk; 11Department of Medicine, Norfolk Spot, Imperial College London, London W2 1PG, United kingdom; 12MRC National Institute for Medical Research, London, United kingdom; and 13Institute for Life Sciences, University of Southampton, Southampton, United KingdomBackground. Tuberculosis is transmitted by individuals with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in tuberculosis but the resulting matrix degradation merchandise (MDPs) have not been studied. We investigate the hypothesis that MMP activity generates matrix turnover solutions as correlates of lung pathology. Procedures. Induced sputum and plasma have been collected prospectively from human immunodeficiency virus (HIV) good and unfavorable patients with pulmonary tuberculosis and controls. Concentrations of MDPs and MMPs had been analyzed by ELISA and Luminex array in 2 patient cohorts. Outcomes. Procollagen III N-terminal propeptide (PIIINP) was three.8-fold larger in induced sputum of HIVuninfected tuberculosis individuals compared to controls and desmosine, released during elastin degradation, was two.4fold higher. PIIINP was elevated in plasma of tuberculosis patients.Camalexin Biological Activity Plasma PIIINP correlated with induced sputum MMP-1 concentrations and radiological scores, demonstrating that circulating MDPs reflect lung destruction.Fmoc-D-Arg(Pbf)-OH web In a second patient cohort of mixed HIV seroprevalence, plasma PIIINP concentration was elevated three.PMID:23460641 0-fold above controls (P .001). Plasma matrix metalloproteinase-8 concentrations had been also greater in tuberculosis individuals (P = .001). Receiver operating characteristic evaluation utilizing these two variables demonstrated an region beneath the curve of 0.832 (P .001). Conclusions. In pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products. Keyword phrases. lung; mycobacteria; immunopathology; extracellular matrix; matrix metalloproteinase.The global tuberculosis pandemic continues in spite of an intense biomedical research work to improve.
