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ADAM17 and related epithelial injury markers in bronchoalveolar lavage and blood distinguish COPD from controls

Lau, Carin E. LU ; van der Burg, Nicole M.D. LU orcid ; Ankerst, Jaro LU orcid ; Bjermer, Leif LU and Tufvesson, Ellen LU (2026) In Respiratory Medicine 251. p.1-10
Abstract

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has many known dysregulated inflammatory proteins. A disintegrin and metalloproteinase 17 (ADAM17) is a protease that sheds several proteins involved in COPD pathogenesis. The aim was to investigate ADAM17, its phosphorylated form (pADAM17) and its substrates in bronchoalveolar lavage (BAL) and blood from COPD and control subjects. METHODS: Groups were matched by sex, age, BMI and smoking status to compare between COPD, smoking and never smoking control subjects. The expression of ADAM17 and pADAM17 was assessed using immunofluorescence in BAL cells (n = 6-13). Concentrations of soluble ADAM17 and its substrates were quantified using ELISA or Luminex in BAL fluid (BALF, n = 11-14)... (More)

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has many known dysregulated inflammatory proteins. A disintegrin and metalloproteinase 17 (ADAM17) is a protease that sheds several proteins involved in COPD pathogenesis. The aim was to investigate ADAM17, its phosphorylated form (pADAM17) and its substrates in bronchoalveolar lavage (BAL) and blood from COPD and control subjects. METHODS: Groups were matched by sex, age, BMI and smoking status to compare between COPD, smoking and never smoking control subjects. The expression of ADAM17 and pADAM17 was assessed using immunofluorescence in BAL cells (n = 6-13). Concentrations of soluble ADAM17 and its substrates were quantified using ELISA or Luminex in BAL fluid (BALF, n = 11-14) and blood (n = 10-30). RESULTS: COPD BAL samples had more ADAM17+ and pADAM17+ cells than controls and intracellular localisations were observed in epithelial cells of subjects with a smoking history. These elevations coincided with higher concentrations of several of the ADAM17 substrates in BALF from Smokers and COPD subjects, most prominently was the increased BALF HB-EGF found in COPD but not Smokers. Other changes in blood were also mostly related to epithelial injury and repair. CONCLUSIONS: Our findings highlight an overabundance of ADAM17 and pADAM17 in COPD airways that is accentuated beyond smoking-induced changes. This broad catalytic-complex analysis has both combined individual biomarkers and discovered more novel disease-specific biomarkers that may all relate to the overarching functionality of ADAM17 in COPD, warranting further investigation into the role this enzyme plays in COPD pathogenesis.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ADAM17, Bronchoalveolar lavage, COPD, Epithelial injury, pADAM17
in
Respiratory Medicine
volume
251
article number
108596
pages
1 - 10
publisher
Elsevier
external identifiers
  • scopus:105026613966
  • pmid:41421560
ISSN
1532-3064
DOI
10.1016/j.rmed.2025.108596
language
English
LU publication?
yes
additional info
Publisher Copyright: Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.
id
442f1780-fc87-4a52-97fb-12c24030c5d7
date added to LUP
2026-01-16 07:33:36
date last changed
2026-01-30 08:53:20
@article{442f1780-fc87-4a52-97fb-12c24030c5d7,
  abstract     = {{<p>BACKGROUND: Chronic obstructive pulmonary disease (COPD) has many known dysregulated inflammatory proteins. A disintegrin and metalloproteinase 17 (ADAM17) is a protease that sheds several proteins involved in COPD pathogenesis. The aim was to investigate ADAM17, its phosphorylated form (pADAM17) and its substrates in bronchoalveolar lavage (BAL) and blood from COPD and control subjects. METHODS: Groups were matched by sex, age, BMI and smoking status to compare between COPD, smoking and never smoking control subjects. The expression of ADAM17 and pADAM17 was assessed using immunofluorescence in BAL cells (n = 6-13). Concentrations of soluble ADAM17 and its substrates were quantified using ELISA or Luminex in BAL fluid (BALF, n = 11-14) and blood (n = 10-30). RESULTS: COPD BAL samples had more ADAM17+ and pADAM17+ cells than controls and intracellular localisations were observed in epithelial cells of subjects with a smoking history. These elevations coincided with higher concentrations of several of the ADAM17 substrates in BALF from Smokers and COPD subjects, most prominently was the increased BALF HB-EGF found in COPD but not Smokers. Other changes in blood were also mostly related to epithelial injury and repair. CONCLUSIONS: Our findings highlight an overabundance of ADAM17 and pADAM17 in COPD airways that is accentuated beyond smoking-induced changes. This broad catalytic-complex analysis has both combined individual biomarkers and discovered more novel disease-specific biomarkers that may all relate to the overarching functionality of ADAM17 in COPD, warranting further investigation into the role this enzyme plays in COPD pathogenesis.</p>}},
  author       = {{Lau, Carin E. and van der Burg, Nicole M.D. and Ankerst, Jaro and Bjermer, Leif and Tufvesson, Ellen}},
  issn         = {{1532-3064}},
  keywords     = {{ADAM17; Bronchoalveolar lavage; COPD; Epithelial injury; pADAM17}},
  language     = {{eng}},
  month        = {{01}},
  pages        = {{1--10}},
  publisher    = {{Elsevier}},
  series       = {{Respiratory Medicine}},
  title        = {{ADAM17 and related epithelial injury markers in bronchoalveolar lavage and blood distinguish COPD from controls}},
  url          = {{http://dx.doi.org/10.1016/j.rmed.2025.108596}},
  doi          = {{10.1016/j.rmed.2025.108596}},
  volume       = {{251}},
  year         = {{2026}},
}