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The depletion of donor macrophages reduces ischaemia-reperfusion injury after mouse lung transplantation†

Tsushima, Yukio ; Jang, Jae-Hwi ; Yamada, Yoshito ; Schwendener, Reto ; Suzuki, Kenji ; Weder, Walter ; Jungraithmayr, Wolfgang

In: European Journal of Cardio-Thoracic Surgery, 2014, vol. 45, no. 4, p. 703-709

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    Titre
    • The depletion of donor macrophages reduces ischaemia-reperfusion injury after mouse lung transplantation†
    Auteur
    • Tsushima, Yukio. Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
    • Jang, Jae-Hwi. Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
    • Yamada, Yoshito. Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
    • Schwendener, Reto. Institute of Molecular Cancer Research, Zurich,Switzerland
    • Suzuki, Kenji. Department of General Thoracic Surgery, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
    • Weder, Walter. Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
    • Jungraithmayr, Wolfgang. Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • European Journal of Cardio-Thoracic Surgery, 2014, vol. 45, no. 4, p. 703-709. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:292153
    Summary
    OBJECTIVES Macrophages (M) are one of the most important cells of the innate immune system for first line defense. Upon transplantation (Tx), M play a prominent role during lung ischaemia reperfusion (I/R) injury. Here, we hypothesize that the depletion of donor M ameliorates the post-transplant lung I/R injury. METHODS Orthotopic single-lung Tx was performed between syngeneic BALB/c mice after a cold ischaemic time of 8 h and a reperfusion time of 10 h. Prior to graft implantation, alveolar macrophages of donor lungs were selectively depleted applying the ‘suicide technique' by intratracheal application of clodronate liposomes (experimental, n = 6) vs the application of empty liposomes (control, n = 6). Cell count (number of F4/80+-macrophages) and graft injury were evaluated by histology and immunohistochemistry, and levels of lactat dehydrogenase (LDH) (apoptosis assay), enzyme linked immunosorbent assay for nuclear protein high-mobility-group-protein B1 (HMGB1), tumor necrosis factor alpha (TNF-α) and transforming growth factor beta1 (TGF-β1) in plasma were analysed. RESULTS Clodronate liposomes successfully reduced 70% of M from donor lungs when compared with grafts treated with empty liposome only. M-depleted transplants showed improved histology and revealed considerably less graft damage when compared with control recipients (LDH, P = 0.03; HMGB1, P = 0.3). Oxygenation capacity was ameliorated in M-depleted transplants, if not significant (P = 0.114); however, wet/dry ratio did not differ between groups (P = 0.629). The inflammatory response was significantly reduced in M-depleted mice when compared with control recipients (TNF-α, P = 0.042; TGF-β1, P = 0.039). CONCLUSIONS The selective depletion of M in donor lung transplants can be successfully performed and results in a sustained anti-inflammatory response upon I/R-injury. The beneficial effect of this preconditioning method should be further evaluated as a promising tool for the attenuation of I/R prior to graft implantation in clinical Tx