The effect of secretory leukocyte protease inhibitor (SLPI) on ischemia/reperfusion injury in cardiac transplantation

S. Schneeberger, T. Hautz, S. M. Wahl, Gerald Brandacher, R. Sucher, O. Steinmassl, P. Steinmassl, C. D. Wright, P. Obrist, E. R. Werner, W. Mark, J. Troppmair, R. Margreiter, A. Amberger

Research output: Contribution to journalArticle

Abstract

We investigated the role of secretory leukocyte protease inhibitor (SLPI) in ischemia/reperfusion injury in cardiac transplantation. SLPI-/- mouse hearts and wild-type (WT) controls were transplanted immediately or after 10 h of cold ischemia (CI). Recombinant SLPI (rSLPI) was added to the preservation solution or given systemically. After evaluation of myocardial performance, grafts were investigated for histology, SLPI, TNF-α, TGF-β, NF-κB and protease expression at indicated time points. Early myocardial contraction was profoundly impaired in SLPI-/- hearts exposed to CI and associated with high intra-graft protease expression. Systemic administration of rSLPI had no effect, however, when SLPI was added to the preservation solution, myocardial contraction was restored to normal. At 10 days, inflammation, myocyte vacuolization and necrosis were significantly more severe in SLPI-/- hearts. SLPI gene expression was detected in WT mice at 12 and 24 h and was significantly higher after CI. SLPI protein was observed at 24 h and 10 days. High intra-graft concentrations of SLPI after administration of rSLPI were inversely correlated with protease levels early and TGF-β expression late after reperfusion. SLPI plays a crucial role in early myocardial performance and postischemic inflammation after cardiac transplantation. A dual inhibitory effect on protease and TGF-β expression might be the underlying mechanism.

Original languageEnglish (US)
Pages (from-to)773-782
Number of pages10
JournalAmerican Journal of Transplantation
Volume8
Issue number4
DOIs
StatePublished - Apr 2008
Externally publishedYes

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Secretory Leukocyte Peptidase Inhibitor
Heart Transplantation
Reperfusion Injury
Cold Ischemia
Peptide Hydrolases
Myocardial Contraction
Transplants
Inflammation
Muscle Cells
Reperfusion

Keywords

  • Heart transplantation
  • Ischemia
  • Reperfusion
  • SLPI

ASJC Scopus subject areas

  • Immunology

Cite this

The effect of secretory leukocyte protease inhibitor (SLPI) on ischemia/reperfusion injury in cardiac transplantation. / Schneeberger, S.; Hautz, T.; Wahl, S. M.; Brandacher, Gerald; Sucher, R.; Steinmassl, O.; Steinmassl, P.; Wright, C. D.; Obrist, P.; Werner, E. R.; Mark, W.; Troppmair, J.; Margreiter, R.; Amberger, A.

In: American Journal of Transplantation, Vol. 8, No. 4, 04.2008, p. 773-782.

Research output: Contribution to journalArticle

Schneeberger, S, Hautz, T, Wahl, SM, Brandacher, G, Sucher, R, Steinmassl, O, Steinmassl, P, Wright, CD, Obrist, P, Werner, ER, Mark, W, Troppmair, J, Margreiter, R & Amberger, A 2008, 'The effect of secretory leukocyte protease inhibitor (SLPI) on ischemia/reperfusion injury in cardiac transplantation', American Journal of Transplantation, vol. 8, no. 4, pp. 773-782. https://doi.org/10.1111/j.1600-6143.2008.02158.x
Schneeberger, S. ; Hautz, T. ; Wahl, S. M. ; Brandacher, Gerald ; Sucher, R. ; Steinmassl, O. ; Steinmassl, P. ; Wright, C. D. ; Obrist, P. ; Werner, E. R. ; Mark, W. ; Troppmair, J. ; Margreiter, R. ; Amberger, A. / The effect of secretory leukocyte protease inhibitor (SLPI) on ischemia/reperfusion injury in cardiac transplantation. In: American Journal of Transplantation. 2008 ; Vol. 8, No. 4. pp. 773-782.
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