Skip to main content
Top
Published in: BMC Pulmonary Medicine 1/2021

Open Access 01-12-2021 | COPD Exacerbation | Research article

Elevated levels of arginase activity are related to inflammation in patients with COPD exacerbation

Authors: Marcel Jose Rodríguez-Guzmán, Germán Peces-Barba Romero, Sandra Pérez Rial, Cristina Serrano del Castillo, Miguel Ángel Palomero Rodríguez, Ignacio Mahillo-Fernandez, Felipe Villar-Álvarez

Published in: BMC Pulmonary Medicine | Issue 1/2021

Login to get access

Abstract

Introduction

Within the pathogenesis of the chronic obstructive pulmonary disease (COPD) there are interactions between different inflammatory mediators that are enhanced during an exacerbation. Arginase is present in bronchial epithelial cells, endothelial, fibroblasts and alveolar macrophages, which make it a probable key enzyme in the regulation of inflammation and remodelling. We aimed to find a potential relationship between arginase activity, inflammatory mediators in COPD patients in stable phase and during exacerbations.

Methods

We performed a prospective, observational study of cases and controls, with 4 study groups (healthy controls, stable COPD, COPD during an exacerbation and COPD 3 months after exacerbation). We measured arginase, inflammation markers (IL-6, IL-8, TNF-∝, IFN-γ and C reactive protein), and mediators of immunity: neutrophils, monocytes, total TCD3 + lymphocytes (CD3ζ), CD4 + T cells, CD8 + T cells, NK cells.

Results

A total of 49 subjects were recruited, average age of 69.73 years (59.18% male). Arginase activity is elevated during an exacerbation of COPD, and this rise is related to an increase in IL-6 production. The levels of IL-6 and IL-8 remained elevated in patients with COPD at 3 months after hospital exacerbation.
We did not find a clear relationship between arginase activity, immunity or with the degree of obstruction in COPD patients.

Conclusions

Arginase activity is elevated during an exacerbation of COPD, and it could be related to an increase in the production of IL-6. Levels of IL-6, IL-8, and arginase activity remain elevated in patients with COPD at 3 months after hospital exacerbation. Arginase activity could contribute to the development of COPD.
Literature
2.
go back to reference Del Puerto-Nevado L, Pérez-Ria P, Girón-Martínez A, Peces-Barba G. Papel de la inflamación en la etiopatogenia de la EPOC. Arch Bronconeumol 2010; 46(Supl.11):2–7. Del Puerto-Nevado L, Pérez-Ria P, Girón-Martínez A, Peces-Barba G. Papel de la inflamación en la etiopatogenia de la EPOC. Arch Bronconeumol 2010; 46(Supl.11):2–7.
3.
go back to reference Piehl-Aulin K, Jones I, Lindvall B, Magnuson A, Abdel-Halim SM. Increased serum inflammatory markers in the absence of clinical and skeletal muscle inflammation in patients with chronic obstructive pulmonary disease. Respiration. 2009;78(2):191–6.CrossRef Piehl-Aulin K, Jones I, Lindvall B, Magnuson A, Abdel-Halim SM. Increased serum inflammatory markers in the absence of clinical and skeletal muscle inflammation in patients with chronic obstructive pulmonary disease. Respiration. 2009;78(2):191–6.CrossRef
4.
go back to reference Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J. 2003;22(4):672–88.CrossRef Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J. 2003;22(4):672–88.CrossRef
5.
go back to reference Wang Z, Zheng T, Zhu Z, Homer R, Riese R, Chapman H, et al. Interferon gamma induction of pulmonary emphysema in the adult murine lung. J Exp Med. 2000;192(11):1587–600.CrossRef Wang Z, Zheng T, Zhu Z, Homer R, Riese R, Chapman H, et al. Interferon gamma induction of pulmonary emphysema in the adult murine lung. J Exp Med. 2000;192(11):1587–600.CrossRef
6.
go back to reference Martínez García MA, Soler Cataluña JJ. EPOC y bronquiectasias. Arch Bronconeumol 2010; 46(Supl.3): 11–7. Martínez García MA, Soler Cataluña JJ. EPOC y bronquiectasias. Arch Bronconeumol 2010; 46(Supl.3): 11–7.
7.
go back to reference Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet. 2007;370(9589):786–96.CrossRef Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet. 2007;370(9589):786–96.CrossRef
8.
go back to reference Hurst JR, Donaldson GC, Perera WR, Wilkinson TM, Bilello JA, Hagan GW, et al. Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J RespirCrit Care Med. 2006;174:867–74.CrossRef Hurst JR, Donaldson GC, Perera WR, Wilkinson TM, Bilello JA, Hagan GW, et al. Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J RespirCrit Care Med. 2006;174:867–74.CrossRef
9.
go back to reference Karadag F, Karul AB, Cildag O, Yilmaz M, Ozcan H. Biomarkers of systemic inflammation in stable and exacerbation phases of COPD. Lung. 2008;186(6):403–9.CrossRef Karadag F, Karul AB, Cildag O, Yilmaz M, Ozcan H. Biomarkers of systemic inflammation in stable and exacerbation phases of COPD. Lung. 2008;186(6):403–9.CrossRef
11.
go back to reference Munder M, Mollinedo F, Calafat J, Canchado J, Gil-Lamaignere C, Fuentes JM, et al. Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity. Blood. 2005;105(6):2549–56.CrossRef Munder M, Mollinedo F, Calafat J, Canchado J, Gil-Lamaignere C, Fuentes JM, et al. Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity. Blood. 2005;105(6):2549–56.CrossRef
12.
go back to reference Munder M. Arginase: an emerging key player in the mammalian immune system. Br J Pharmacol;158(3):638–51. Munder M. Arginase: an emerging key player in the mammalian immune system. Br J Pharmacol;158(3):638–51.
13.
go back to reference Ochoa JB, Bernard AC, O`Brin WE. Arginase I expression and activity in human mononuclear cells after injury. Ann Surg 2001; 233: 393–97. Ochoa JB, Bernard AC, O`Brin WE. Arginase I expression and activity in human mononuclear cells after injury. Ann Surg 2001; 233: 393–97.
14.
go back to reference Tadié JM, Henno P, Leroy I, Danel C, Naline E, Faisy C, et al. Role of nitric oxide synthase/arginase balance in bronchial reactivity in patients with chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 2008;294(3):L489–97.CrossRef Tadié JM, Henno P, Leroy I, Danel C, Naline E, Faisy C, et al. Role of nitric oxide synthase/arginase balance in bronchial reactivity in patients with chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 2008;294(3):L489–97.CrossRef
15.
go back to reference Maarsingh H, Pera T, Meurs H. Arginase and pulmonary diseases. Naunyn-Schmiedberg’s Arch Pharmacol. 2008;378:171–84.CrossRef Maarsingh H, Pera T, Meurs H. Arginase and pulmonary diseases. Naunyn-Schmiedberg’s Arch Pharmacol. 2008;378:171–84.CrossRef
17.
go back to reference Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999;54:581–6.CrossRef Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999;54:581–6.CrossRef
18.
go back to reference P.W. Jones, G. Harding, P. Berry, I. Wiklund, W-H. Chen and N. Kline Leidy. Development and first validation of the COPD Assessment Test. Eur Respir J 2009, 34: 648–654. P.W. Jones, G. Harding, P. Berry, I. Wiklund, W-H. Chen and N. Kline Leidy. Development and first validation of the COPD Assessment Test. Eur Respir J 2009, 34: 648–654.
19.
go back to reference Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Series “ATS/ERS task force: standardisation of lung function testing”: Standardisation of spirometry. Eur Respir J. 2005;26(2):319–38.CrossRef Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Series “ATS/ERS task force: standardisation of lung function testing”: Standardisation of spirometry. Eur Respir J. 2005;26(2):319–38.CrossRef
20.
go back to reference Garcia Navas, R. Papel inmunosupresor y citotóxico de la arginasa I y la disponibilidad de L-arginina en el sistema inmune y cáncer. Tesis doctoral. Salamanca. Centro de Investigación del Cáncer – CSIC, Facultad de Medicina, Universidad de Salamanca; 2014. Garcia Navas, R. Papel inmunosupresor y citotóxico de la arginasa I y la disponibilidad de L-arginina en el sistema inmune y cáncer. Tesis doctoral. Salamanca. Centro de Investigación del Cáncer – CSIC, Facultad de Medicina, Universidad de Salamanca; 2014.
22.
go back to reference Gutierrez P, Closa D, Piñer R, Bulbuena O, Menéndez R, torres A. Macrophage activation in exacerbated COPD with and without community-acquired pneumonia. Eur Respir J 2010; 36: 285–291. Gutierrez P, Closa D, Piñer R, Bulbuena O, Menéndez R, torres A. Macrophage activation in exacerbated COPD with and without community-acquired pneumonia. Eur Respir J 2010; 36: 285–291.
23.
go back to reference Ruzsics I, Nagy L, Keki S, Sarosi V, Illes B, Illes Z, et al. L-arginine pathway in COPD patients with acute exacerbation: a new potential biomarker. COPD. 2016;13(2):139–45.CrossRef Ruzsics I, Nagy L, Keki S, Sarosi V, Illes B, Illes Z, et al. L-arginine pathway in COPD patients with acute exacerbation: a new potential biomarker. COPD. 2016;13(2):139–45.CrossRef
24.
go back to reference Molnar T, Pusch G, Nagy L, Keki S, Berki T, Illes Z. Correlation of the L-arginine pathway with thrombo-inflammation may contribute to the outcome of acute ischemic stroke. J Stroke Cerebrovasc Dis. 2016;25(8):2055–60.CrossRef Molnar T, Pusch G, Nagy L, Keki S, Berki T, Illes Z. Correlation of the L-arginine pathway with thrombo-inflammation may contribute to the outcome of acute ischemic stroke. J Stroke Cerebrovasc Dis. 2016;25(8):2055–60.CrossRef
25.
go back to reference Scrimini S, Pons J, Agustí A, Soriano JB, Cosio BG, Torrecilla JA, et al. Differential effects of smoking and COPD upon circulatin myeloid derived suppressor cells. Respir Med. 2013;107(12):1895–903.CrossRef Scrimini S, Pons J, Agustí A, Soriano JB, Cosio BG, Torrecilla JA, et al. Differential effects of smoking and COPD upon circulatin myeloid derived suppressor cells. Respir Med. 2013;107(12):1895–903.CrossRef
26.
go back to reference Diehl S, Rincón M. The two faces of IL-6 on Th1/Th2 differentiation. Mol Immunol. 2002;39(9):531–6.CrossRef Diehl S, Rincón M. The two faces of IL-6 on Th1/Th2 differentiation. Mol Immunol. 2002;39(9):531–6.CrossRef
27.
28.
go back to reference Pera T, Zuidhof AB, Smit M, Menzen MH, Klein T, Flik G, et al. Arginase inhibition prevents inflammation and remodeling in a guinea pig model of chronic obstructive pulmonary disease. J Pharmacol Exp Ther. 2014;349(2):229–38.CrossRef Pera T, Zuidhof AB, Smit M, Menzen MH, Klein T, Flik G, et al. Arginase inhibition prevents inflammation and remodeling in a guinea pig model of chronic obstructive pulmonary disease. J Pharmacol Exp Ther. 2014;349(2):229–38.CrossRef
29.
go back to reference Maarsingh H, Zuidhof A. Arginase inhibition protects against allergen-induced airway obstruction, hyperresponsiveness and inflammation. Am J Respir Crit Care Med. 2008;178:565–73.CrossRef Maarsingh H, Zuidhof A. Arginase inhibition protects against allergen-induced airway obstruction, hyperresponsiveness and inflammation. Am J Respir Crit Care Med. 2008;178:565–73.CrossRef
30.
go back to reference Bergeron C, Boulet LP, Page N, Laviolette M, Zimmermann N, Rothenberg ME, et al. Influence of cigarette smoke on the arginine pathway in asthmatic airways: increased expression of arginase I. J Allergy Clin Immunol. 2007;119(2):391–7.CrossRef Bergeron C, Boulet LP, Page N, Laviolette M, Zimmermann N, Rothenberg ME, et al. Influence of cigarette smoke on the arginine pathway in asthmatic airways: increased expression of arginase I. J Allergy Clin Immunol. 2007;119(2):391–7.CrossRef
31.
go back to reference Jonker R, Deutz NE, Erbland ML, Anderson PJ, Engelen MP. Alterations in whole-body arginine metabolism in chronic obstructive pulmonary disease. Am J Clin Nutr. 2016;103(6):1458–64.CrossRef Jonker R, Deutz NE, Erbland ML, Anderson PJ, Engelen MP. Alterations in whole-body arginine metabolism in chronic obstructive pulmonary disease. Am J Clin Nutr. 2016;103(6):1458–64.CrossRef
32.
go back to reference Zinellu A, Fois AG, Sotgia S, Sotgiu E, Zinellu E, Bifulco F et al. Arginines plasma concentration and oxidative stress in mild to moderate COPD. PLoS ONE 2016;11(8):e0160237. Zinellu A, Fois AG, Sotgia S, Sotgiu E, Zinellu E, Bifulco F et al. Arginines plasma concentration and oxidative stress in mild to moderate COPD. PLoS ONE 2016;11(8):e0160237.
Metadata
Title
Elevated levels of arginase activity are related to inflammation in patients with COPD exacerbation
Authors
Marcel Jose Rodríguez-Guzmán
Germán Peces-Barba Romero
Sandra Pérez Rial
Cristina Serrano del Castillo
Miguel Ángel Palomero Rodríguez
Ignacio Mahillo-Fernandez
Felipe Villar-Álvarez
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2021
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-021-01629-w

Other articles of this Issue 1/2021

BMC Pulmonary Medicine 1/2021 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.