The Calprotectin Fragment, CPa9-HNE, Is a Plasma Biomarker of Mild Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease predominantly of the small airways and parenchyma. COPD lungs exhibit an influx of circulating innate immune cells, which, when isolated, display impaired functions, including imbalanced protease secretion. In addition to...
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2025-07-01
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| author | Mugdha M. Joglekar Jannie M. B. Sand Theo Borghuis Diana J. Leeming Morten Karsdal Frank Klont Russell P. Bowler Barbro N. Melgert Janette K. Burgess Simon D. Pouwels |
| author_facet | Mugdha M. Joglekar Jannie M. B. Sand Theo Borghuis Diana J. Leeming Morten Karsdal Frank Klont Russell P. Bowler Barbro N. Melgert Janette K. Burgess Simon D. Pouwels |
| author_sort | Mugdha M. Joglekar |
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| description | Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease predominantly of the small airways and parenchyma. COPD lungs exhibit an influx of circulating innate immune cells, which, when isolated, display impaired functions, including imbalanced protease secretion. In addition to immune cells, the extracellular matrix (ECM) plays a crucial role in COPD pathology. Remodeling of the ECM can generate ECM fragments, which can be released into circulation and subsequently induce pro-inflammatory responses. COPD is a heterogeneous disease, and serological biomarkers can be used to sub-categorize COPD patients for targeted treatments and optimal recruitment in clinical trials. This study evaluated fragments of calprotectin, collagen type VI, and versican, generated by neutrophil elastase and matrix metalloproteinases (MMP-) 2 and 12, respectively, as potential biomarkers of COPD disease, severity, and endotypes. Lower plasma levels of a neoepitope marker of calprotectin, indicative of activated neutrophils (nordicCPa9-HNETM), were detected in COPD donors compared to controls. CPa9-HNE was associated with milder disease, higher degree of air-trapping, and higher serum levels of MMP-2. Deposition of CPa9-HNE levels in lung tissue revealed no differences between groups. Taken together, CPa9-HNE was found to be a potential marker of mild COPD, but further studies are warranted to validate our findings. |
| format | Article |
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| institution | DOAJ |
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| language | English |
| publishDate | 2025-07-01 |
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| series | Cells |
| spelling | doaj-art-a2c1c15e207f48a681f5f3ebba758e4c2025-08-20T03:02:55ZengMDPI AGCells2073-44092025-07-011415115510.3390/cells14151155The Calprotectin Fragment, CPa9-HNE, Is a Plasma Biomarker of Mild Chronic Obstructive Pulmonary DiseaseMugdha M. Joglekar0Jannie M. B. Sand1Theo Borghuis2Diana J. Leeming3Morten Karsdal4Frank Klont5Russell P. Bowler6Barbro N. Melgert7Janette K. Burgess8Simon D. Pouwels9Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsNordic Bioscience A/S, 2730 Herlev, DenmarkDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsNordic Bioscience A/S, 2730 Herlev, DenmarkNordic Bioscience A/S, 2730 Herlev, DenmarkDepartment of Pharmacotherapy, Epidemiology, and Economics, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDivision of Pulmonary Medicine, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USAGroningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsChronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease predominantly of the small airways and parenchyma. COPD lungs exhibit an influx of circulating innate immune cells, which, when isolated, display impaired functions, including imbalanced protease secretion. In addition to immune cells, the extracellular matrix (ECM) plays a crucial role in COPD pathology. Remodeling of the ECM can generate ECM fragments, which can be released into circulation and subsequently induce pro-inflammatory responses. COPD is a heterogeneous disease, and serological biomarkers can be used to sub-categorize COPD patients for targeted treatments and optimal recruitment in clinical trials. This study evaluated fragments of calprotectin, collagen type VI, and versican, generated by neutrophil elastase and matrix metalloproteinases (MMP-) 2 and 12, respectively, as potential biomarkers of COPD disease, severity, and endotypes. Lower plasma levels of a neoepitope marker of calprotectin, indicative of activated neutrophils (nordicCPa9-HNETM), were detected in COPD donors compared to controls. CPa9-HNE was associated with milder disease, higher degree of air-trapping, and higher serum levels of MMP-2. Deposition of CPa9-HNE levels in lung tissue revealed no differences between groups. Taken together, CPa9-HNE was found to be a potential marker of mild COPD, but further studies are warranted to validate our findings.https://www.mdpi.com/2073-4409/14/15/1155COPDbiomarkersECM fragmentsCPa9-HNES100A9DAMPs |
| spellingShingle | Mugdha M. Joglekar Jannie M. B. Sand Theo Borghuis Diana J. Leeming Morten Karsdal Frank Klont Russell P. Bowler Barbro N. Melgert Janette K. Burgess Simon D. Pouwels The Calprotectin Fragment, CPa9-HNE, Is a Plasma Biomarker of Mild Chronic Obstructive Pulmonary Disease Cells COPD biomarkers ECM fragments CPa9-HNE S100A9 DAMPs |
| title | The Calprotectin Fragment, CPa9-HNE, Is a Plasma Biomarker of Mild Chronic Obstructive Pulmonary Disease |
| title_full | The Calprotectin Fragment, CPa9-HNE, Is a Plasma Biomarker of Mild Chronic Obstructive Pulmonary Disease |
| title_fullStr | The Calprotectin Fragment, CPa9-HNE, Is a Plasma Biomarker of Mild Chronic Obstructive Pulmonary Disease |
| title_full_unstemmed | The Calprotectin Fragment, CPa9-HNE, Is a Plasma Biomarker of Mild Chronic Obstructive Pulmonary Disease |
| title_short | The Calprotectin Fragment, CPa9-HNE, Is a Plasma Biomarker of Mild Chronic Obstructive Pulmonary Disease |
| title_sort | calprotectin fragment cpa9 hne is a plasma biomarker of mild chronic obstructive pulmonary disease |
| topic | COPD biomarkers ECM fragments CPa9-HNE S100A9 DAMPs |
| url | https://www.mdpi.com/2073-4409/14/15/1155 |
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