Date: Sunday, June 2, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: M1 macrophages have been shown to be able to phagocytize dead cells after ischemia-reperfusion injury (IRI). This study investigated the therapeutic effect of CD47 blockade on hepatic macrophage polarization in the setting of normothermic extracorporeal liver perfusion (NELP) of the discarded human livers.
*Methods: The discarded human livers were flushed either with an anti-CD47 monoclonal antibody or IgG control at a dose of 4mg/liver (n=6, respectively). Subsequently, the livers were placed on our extracorporeal machine perfused with blood at 37°C for 6 hours. Perfusate samples were collected at 15 minutes, 1hr, 2hr, 3hr, 4hr, 5hr, and 6hr after reperfusion. Liver biopsies were taken prior and post antibody flush, and at the end of NELP for further analysis.
*Results: We observed an increase of CD80 positive cells (M1) in the CD47mAb treated livers in comparison to the livers in the control group after 6 hours NELP (Figure 1), which was confirmed by Western blots and densitometry analysis (P=0.008). The CD206 positive cells (M2-like) were also marginally decreased in the CD47mAb group compared to the control group at hour 6 (P=0.075). Pathological analysis of the hepatic vacuolization and necrosis found no significant difference between the treatment and control groups (P=0.095, Mann-Whitney U test). The ALT and AST levels were highly variable at 1 hour after machine perfusion and no significant differences were found in the perfusate chemistry study (Data not shown).
*Conclusions: These results demonstrate that the CD47mAb treatment can promote the M1 polarization of hepatic macrophages, suggesting a mechanism for rehabilitating marginal liver grafts via NELP for transplantation.
To cite this abstract in AMA style:Xu M, Zhou F, Garcia-Aroz S, Banan B, Yang W, Upadhya G, Byrnes K, Wong B, Manning P, Lin Y, Chapman W. CD47 Blockade Promotes Hepatic Macrophage Polarization toward M1 during Normothermic Machine Perfusion of Discarded Human Livers [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/cd47-blockade-promotes-hepatic-macrophage-polarization-toward-m1-during-normothermic-machine-perfusion-of-discarded-human-livers/. Accessed August 10, 2020.
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