dc.contributor.author
Carstens, Henning
dc.contributor.author
Kalka, Katharina
dc.contributor.author
Verhaegh, Rabea
dc.contributor.author
Schumacher, Fabian
dc.contributor.author
Soddemann, Matthias
dc.contributor.author
Wilker, Barbara
dc.contributor.author
Keitsch, Simone
dc.contributor.author
Sehl, Carolin
dc.contributor.author
Kleuser, Burkhard
dc.contributor.author
Wahlers, Thorsten
dc.date.accessioned
2021-12-14T14:34:39Z
dc.date.available
2021-12-14T14:34:39Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/33131
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-32853
dc.description.abstract
Ex-vivo lung perfusion (EVLP) systems like XVIVO are more and more common in the setting of lung transplantation, since marginal donor-lungs can easily be subjected to a performance test or be treated with corticosteroids or antibiotics in high dose regimes. Donor lungs are frequently positive in bronchoalveolar lavage (BAL) bacterial cultures (46–89%) which leads to a donor-to-recipient transmission and after a higher risk of lung infection with reduced posttransplant outcome. We have previously shown that sphingosine very efficiently kills a variety of pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus and epidermidis, Escherichia coli or Haemophilus influenzae. Thus, sphingosine could be a new treatment option with broadspectrum antiinfective potential, which may improve outcome after lung transplantation when administered prior to lung re-implantation. Here, we tested whether sphingosine has any adverse effects in the respiratory tract when applied into isolated ventilated and perfused lungs. A 4-h EVLP run using minipig lungs was performed. Functional parameters as well as perfusate measurements where obtained. Biopsies were obtained 30 min and 150 min after inhalation of sphingosine. Tissue samples were fixed in paraformaldehyde, embedded in paraffin and sectioned. Hemalaun, TUNEL as well as stainings with Cy3-coupled anti-sphingosine or anti-ceramide antibodies were implemented. We demonstrate that tube-inhalation of sphingosine into ex-vivo perfused and ventilated minipig lungs results in increased levels of sphingosine in the luminal membrane of bronchi and the trachea without morphological side effects up to very high doses of sphingosine. Sphingosine also did not affect functional lung performance. In summary, the inhalation of sphingosine results in an increase of sphingosine concentrations in the luminal plasma membrane of tracheal and bronchial epithelial cells. The inhalation has no local side effects in ex-vivo perfused and ventilated minipig lungs.
en
dc.format.extent
10 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Drug delivery
en
dc.subject
Infectious diseases
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik
dc.title
Inhaled sphingosine has no adverse side effects in isolated ventilated and perfused pig lungs
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
18607
dcterms.bibliographicCitation.doi
10.1038/s41598-021-97708-3
dcterms.bibliographicCitation.journaltitle
Scientific Reports
dcterms.bibliographicCitation.number
1
dcterms.bibliographicCitation.volume
11
dcterms.bibliographicCitation.url
https://doi.org/10.1038/s41598-021-97708-3
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Pharmazie
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
2045-2322
refubium.resourceType.provider
WoS-Alert