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Citation
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Tsushima Y, Jang J, Yamada Y, Schwendener R, Suzuki K, Weder W, Jungraithmayr W. Eur. J. Cardiothorac. Surg. 2014; 45(4): 703-709. |
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Abstract
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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 antiinflammatory 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. © The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Language: en |
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Keywords
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Male; male; Animals; Lung; immunohistochemistry; Mice; Cytokines; article; comparative study; controlled study; priority journal; nonhuman; transplantation; mouse; lung; animal experiment; blood; animal model; protein blood level; donor; Transplantation; metabolism; lactate dehydrogenase; tumor necrosis factor alpha; cytokine; animal; homeostasis; cytokine production; cell damage; cell count; depletion; clodronic acid; enzyme linked immunosorbent assay; oxygenation; lung transplantation; Transplants; lung injury; cytology; lactate dehydrogenase blood level; transforming growth factor beta1; reperfusion injury; Reperfusion Injury; Bagg albino mouse; Mice, Inbred BALB C; Clodronic Acid; liposome; Liposomes; high mobility group B1 protein; Ischaemia-reperfusion injury; lung alveolus macrophage; Lung Transplantation; Macrophage depletion; Macrophages, Alveolar; Mouse |