Universität zu Köln

Carstens, Henning, Kalka, Katharina, Verhaegh, Rabea, Schumacher, Fabian ORCID: 0000-0001-8703-3275, Soddemann, Matthias, Wilker, Barbara, Keitsch, Simone, Sehl, Carolin, Kleuser, Burkhard, Wahlers, Thorsten, Reiner, Gerald, Koch, Achim, Rauen, Ursula, Gulbins, Erich and Kamler, Markus (2021). Inhaled sphingosine has no adverse side effects in isolated ventilated and perfused pig lungs. Sci Rep, 11 (1). BERLIN: NATURE PORTFOLIO. ISSN 2045-2322

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Carstens, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalka, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Verhaegh, Rabea UNSPECIFIED UNSPECIFIED UNSPECIFIED Schumacher, Fabian UNSPECIFIED orcid.org/0000-0001-8703-3275 UNSPECIFIED Soddemann, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilker, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Keitsch, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Sehl, Carolin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleuser, Burkhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Wahlers, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Reiner, Gerald UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Achim UNSPECIFIED UNSPECIFIED UNSPECIFIED Rauen, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Gulbins, Erich UNSPECIFIED UNSPECIFIED UNSPECIFIED Kamler, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-596978
DOI:	10.1038/s41598-021-97708-3
Journal or Publication Title:	Sci Rep
Volume:	11
Number:	1
Date:	2021
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PSEUDOMONAS-AERUGINOSA; CERAMIDE; INFECTION; INFLAMMATION; SUSCEPTIBILITY; DEATH Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59697