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Korkmaz-Icöz, S.* ; Szabo, G.* ; Gieldon, A.* ; McDonald, P.P.* ; Dashkevich, A.* ; Yildirim, A.Ö. ; Korkmaz, B.*

Protective effects of neutrophil serine protease inhibition against ischemia-reperfusion injury in lung or heart transplantation.

FEBS J., DOI: 10.1111/febs.17411 (2025)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Transplanted organs are inevitably exposed to ischemia-reperfusion (IR) injury, which is known to cause graft dysfunction. Functional and structural changes that follow IR tissue injury are mediated by neutrophils through the production of oxygen-derived free radicals, as well as from degranulation which entails the release of proteases and other pro-inflammatory mediators. Neutrophil serine proteases (NSPs) are believed to be the principal triggers of post-ischemic reperfusion damage. Extended preservation times for the transplanted donor organ correlate with heightened occurrences of vascular damage and graft dysfunction. Preservation with α1-antitrypsin, an endogenous inhibitor of NSPs, improves primary graft function after lung or heart transplantation. Furthermore, pre-operative pharmacological targeting of NSP activation in the recipient using chemical inhibitors suppresses neutrophilic inflammation in transplanted organs. Hence, effective control of NSPs in the graft and recipient is a promising strategy to prevent IR injury. In this review, we describe the pathological functions of NSPs in IR injury and discuss their pharmacological inhibition to prevent primary graft dysfunction in lung or heart transplantation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Korrespondenzautor
Schlagwörter Cathepsin C ; Elastase ; Heart ; Inflammation ; Ischemia–reperfusion Injury ; Lung ; Neutrophil ; Therapeutic Approach; Pharmacological Inhibition; Graft Function; Preservation
ISSN (print) / ISBN 1742-464X
e-ISSN 1742-4658
Zeitschrift FEBS Journal, The
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)
Förderungen Région Centre-Val de Loire
Alexandre von Humboldt Foundation
LE STUDIUM Loire Valley Institute for Advanced Studies for Research Consortium