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Midkine is expressed and differentially processed during COPD exacerbations and ventilator-associated pneumonia associated with Staphylococcus aureus infection.

Linge, Helena LU ; Andersson, Cecilia LU ; Nordin, Sara LU ; Olin, Anders LU ; Petersson, Ann-Cathrine; Mörgelin, Matthias LU ; Welin, Amanda; Bylund, Johan; Bjermer, Leif LU and Erjefält, Jonas LU , et al. (2013) In Molecular Medicine 19(Sep 12). p.314-323
Abstract
Staphylococcus aureus is sometimes isolated from the airways during acute exacerbations of chronic obstructive pulmonary disease (COPD) but more commonly recognized as a cause of ventilator-associated pneumonia (VAP). Antimicrobial proteins, among them midkine (MK), are an important part of innate immunity in the airways. In this study, the levels and possible processing of MK in relation to S. aureus infection of the airways were investigated, comparing COPD and VAP, thus comparing a state of disease with preceding chronic inflammation and remodeling (COPD) with acute inflammation (i.e. VAP). MK was detected in the small airways and alveoli of COPD lung tissue but less so in normal lung tissue. MK at below micromolar concentrations killed... (More)
Staphylococcus aureus is sometimes isolated from the airways during acute exacerbations of chronic obstructive pulmonary disease (COPD) but more commonly recognized as a cause of ventilator-associated pneumonia (VAP). Antimicrobial proteins, among them midkine (MK), are an important part of innate immunity in the airways. In this study, the levels and possible processing of MK in relation to S. aureus infection of the airways were investigated, comparing COPD and VAP, thus comparing a state of disease with preceding chronic inflammation and remodeling (COPD) with acute inflammation (i.e. VAP). MK was detected in the small airways and alveoli of COPD lung tissue but less so in normal lung tissue. MK at below micromolar concentrations killed S. aureus in vitro. Proteolytic processing of MK by the staphylococcal metalloprotease AL but not cysteine protease SA, resulted in impaired bactericidal activity. Degradation was foremost seen in the COOH-terminal portion of the molecule that harbors high bactericidal activity. In addition, MK was detected in sputum from patients suffering from VAP caused by S. aureus but less so in sputum from COPD-exacerbations associated with the same bacterium. Recombinant MK was degraded more rapidly in sputum from the COPD patients than from the VAP patients and a greater proteolytic activity in COPD sputum was confirmed by zymography. Taken together, proteases of both bacteria and the host contribute to degradation of the antibacterial protein MK, resulting in an impaired defense of the airways, in particular in COPD where the state of chronic inflammation could be of importance. (Less)
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Molecular Medicine
volume
19
issue
Sep 12
pages
314 - 323
publisher
The Feinstein Institute for Medical Research
external identifiers
  • wos:000328604700017
  • pmid:24043271
  • scopus:84884874548
ISSN
1528-3658
DOI
10.2119/molmed.2013.00045
language
English
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yes
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6c765961-8023-4ae7-878f-07cc55031e69 (old id 4065724)
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http://www.ncbi.nlm.nih.gov/pubmed/24043271?dopt=Abstract
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2013-10-02 20:37:09
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2019-02-20 01:47:37
@article{6c765961-8023-4ae7-878f-07cc55031e69,
  abstract     = {Staphylococcus aureus is sometimes isolated from the airways during acute exacerbations of chronic obstructive pulmonary disease (COPD) but more commonly recognized as a cause of ventilator-associated pneumonia (VAP). Antimicrobial proteins, among them midkine (MK), are an important part of innate immunity in the airways. In this study, the levels and possible processing of MK in relation to S. aureus infection of the airways were investigated, comparing COPD and VAP, thus comparing a state of disease with preceding chronic inflammation and remodeling (COPD) with acute inflammation (i.e. VAP). MK was detected in the small airways and alveoli of COPD lung tissue but less so in normal lung tissue. MK at below micromolar concentrations killed S. aureus in vitro. Proteolytic processing of MK by the staphylococcal metalloprotease AL but not cysteine protease SA, resulted in impaired bactericidal activity. Degradation was foremost seen in the COOH-terminal portion of the molecule that harbors high bactericidal activity. In addition, MK was detected in sputum from patients suffering from VAP caused by S. aureus but less so in sputum from COPD-exacerbations associated with the same bacterium. Recombinant MK was degraded more rapidly in sputum from the COPD patients than from the VAP patients and a greater proteolytic activity in COPD sputum was confirmed by zymography. Taken together, proteases of both bacteria and the host contribute to degradation of the antibacterial protein MK, resulting in an impaired defense of the airways, in particular in COPD where the state of chronic inflammation could be of importance.},
  author       = {Linge, Helena and Andersson, Cecilia and Nordin, Sara and Olin, Anders and Petersson, Ann-Cathrine and Mörgelin, Matthias and Welin, Amanda and Bylund, Johan and Bjermer, Leif and Erjefält, Jonas and Egesten, Arne},
  issn         = {1528-3658},
  language     = {eng},
  number       = {Sep 12},
  pages        = {314--323},
  publisher    = {The Feinstein Institute for Medical Research},
  series       = {Molecular Medicine},
  title        = {Midkine is expressed and differentially processed during COPD exacerbations and ventilator-associated pneumonia associated with Staphylococcus aureus infection.},
  url          = {http://dx.doi.org/10.2119/molmed.2013.00045},
  volume       = {19},
  year         = {2013},
}