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

作者：Tsushima Yukio; Jang Jae Hwi; Yamada Yoshito; Schwendener Reto; Suzuki Kenji; Weder Walter; Jungraithmayr Wolfgang^*

来源：European Journal of Cardio-Thoracic Surgery, 2014, 45(4): 703-709.

DOI：10.1093/ejcts/ezt489

• Mouse
• Lung
• Transplantation
• Macrophage depletion
• Ischaemia-reperfusion injury

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. %26lt;br%26gt;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 %26apos;suicide technique%26apos; 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-alpha) and transforming growth factor beta1 (TGF-beta 1) in plasma were analysed. %26lt;br%26gt;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-alpha, P = 0.042; TGF-beta 1, P = 0.039). %26lt;br%26gt;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.

• 出版日期2014-4