Priya Sakthivel1,2, Angele Breithaupt3, Marcus Gereke4,5, David A Copland6,7,8, Christian Schulz9, Achim D Gruber3, Andrew D Dick6,7,8, Jens Schreiber10, Dunja Bruder4,5. 1. Immune Regulation Group, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Braunschweig, Germany. priya.sakthivel@helmholtz-hzi.de. 2. Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. priya.sakthivel@helmholtz-hzi.de. 3. Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany. 4. Immune Regulation Group, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Braunschweig, Germany. 5. Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. 6. School of Clinical Sciences, University of Bristol, Bristol, BS8 1TD, UK. 7. School of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD, UK. 8. National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, EC1V 2PD, UK. 9. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University Magdeburg, University Hospital, Magdeburg, Germany. 10. Department of Pulmonology, Otto-von-Guericke-University Magdeburg, University Hospital, Magdeburg, Germany.
Abstract
BACKGROUND: COPD represents a multifactorial lung disorder with high morbidity and mortality. Despite intensive research concerning the underlying disease mechanisms, the involvement of the CD200/CD200R axis in supporting or preventing the onset of COPD has not yet been addressed. Since the CD200/CD200R axis is crucially implicated in the maintenance of pulmonary immune homeostasis, we hypothesized that it might be involved in controlling the onset of COPD. METHODS: To address this, we analyzed the serum samples from COPD patients and normal controls for soluble (s) CD200 and correlated the data to COPD-relevant clinical parameters. In addition, basic studies were conducted in CD200-deficient and wild-type mice in which COPD-like inflammation was induced with elastase/LPS followed by lung and serum component analysis. RESULTS: We observed a positive correlation between serum sCD200 and IL-6 levels as well as a trend toward a negative correlation of sCD200 with vitamin D3 in COPD patients. Further investigations in mice revealed that despite elevated serum concentration of MMP-9 in CD200KO mice, the early onset of COPD-like lung inflammation was similar in CD200-deficient and wild-type animals in terms of immune cell infiltration, emphysematous changes, and mucus overproduction. CONCLUSIONS: While our murine studies suggest that the co-inhibitory molecule CD200 does not appear to play a prominent role in the early onset of COPD-like features, correlation of sCD200 serum levels with COPD-related parameters in humans with established disease revealed that the CD200/CD200R axis may be mechanistically linked to the disease course in COPD patients.
BACKGROUND:COPD represents a multifactorial lung disorder with high morbidity and mortality. Despite intensive research concerning the underlying disease mechanisms, the involvement of the CD200/CD200R axis in supporting or preventing the onset of COPD has not yet been addressed. Since the CD200/CD200R axis is crucially implicated in the maintenance of pulmonary immune homeostasis, we hypothesized that it might be involved in controlling the onset of COPD. METHODS: To address this, we analyzed the serum samples from COPDpatients and normal controls for soluble (s) CD200 and correlated the data to COPD-relevant clinical parameters. In addition, basic studies were conducted in CD200-deficient and wild-type mice in which COPD-like inflammation was induced with elastase/LPS followed by lung and serum component analysis. RESULTS: We observed a positive correlation between serum sCD200 and IL-6 levels as well as a trend toward a negative correlation of sCD200 with vitamin D3 in COPDpatients. Further investigations in mice revealed that despite elevated serum concentration of MMP-9 in CD200KO mice, the early onset of COPD-like lung inflammation was similar in CD200-deficient and wild-type animals in terms of immune cell infiltration, emphysematous changes, and mucus overproduction. CONCLUSIONS: While our murine studies suggest that the co-inhibitory molecule CD200 does not appear to play a prominent role in the early onset of COPD-like features, correlation of sCD200 serum levels with COPD-related parameters in humans with established disease revealed that the CD200/CD200R axis may be mechanistically linked to the disease course in COPDpatients.
Authors: R M Hoek; S R Ruuls; C A Murphy; G J Wright; R Goddard; S M Zurawski; B Blom; M E Homola; W J Streit; M H Brown; A N Barclay; J D Sedgwick Journal: Science Date: 2000-12-01 Impact factor: 47.728
Authors: M E Muroski; M D Roycik; R G Newcomer; P E Van den Steen; G Opdenakker; H R Monroe; Z J Sahab; Q-X Sang Journal: Curr Pharm Biotechnol Date: 2008-02 Impact factor: 2.837
Authors: Umadevi Sajjan; Shyamala Ganesan; Adam T Comstock; Jee Shim; Qiong Wang; Deepti R Nagarkar; Ying Zhao; Adam M Goldsmith; Joanne Sonstein; Marisa J Linn; Jeffrey L Curtis; Marc B Hershenson Journal: Am J Physiol Lung Cell Mol Physiol Date: 2009-09-11 Impact factor: 5.464
Authors: Sarah Dimeloe; David F Richards; Zoe L Urry; Atul Gupta; Victoria Stratigou; Sophie Farooque; Sejal Saglani; Andrew Bush; Catherine M Hawrylowicz Journal: Thorax Date: 2012-02-14 Impact factor: 9.139
Authors: Michał Tomaszewski; Ewelina Grywalska; Weronika Topyła-Putowska; Piotr Błaszczak; Marcin Kurzyna; Jacek Roliński; Grzegorz Kopeć Journal: J Clin Med Date: 2021-03-01 Impact factor: 4.241
Authors: Abdullah Al Mamun; Conelius Ngwa; Shaohua Qi; Pedram Honarpisheh; Saumil Datar; Romana Sharmeen; Yan Xu; Louise D McCullough; Fudong Liu Journal: Stroke Date: 2021-08-06 Impact factor: 10.170