[Purpose] Several efforts have been made to define the mechanisms of accommodation termed as a condition without graft rejection even in the presence of anti-donor antibody. We previously reported the difference in endothelial cell signaling pathways, PI3K/AKT and ERK, between anti-A/B and HLA antibody reaction in vitro accommodation model. However in vivo condition, complement and coagulation system, known as ERK activator, cannot be ignored. AMP-activated protein kinase (AMPK) is an important enzyme as a sensor of cellular energy and has also been reported to have a protective role in endothelial cells. The purpose of this study is to find effective way to navigate accommodation by focusing on AMPK pathway.
[Method] Blood type A-expressing human EA.hy926 endothelial cells were used in this experiment. Resveratrol, AICAR, and Metformin were used as AMPK activators. Complement regulatory protein and HO-1/Ferritin H mRNA expression were measured by flow-cytometry and semi-quantitative RT-PCR, respectively.
[Result] Pre-incubation with complement and thrombin eliminated resistance to complement-mediated cytotoxicity (CDC) induced by anti-A antibody binding to Blood type A-expressing endothelial cells. AMPK activators attenuated CDC about 20 to 50% through the induction CD55, CD59, HO-1, and Ferritin H genes. Resveratrol counteracted the inhibitory effect of complement and thrombin on acquisition of resistance to CDC (about 50%).
[Discussion] AMPK activation was effective for resistance to CDC, in particular ERK activation condition. AMPK regulation in endothelial cells could become the potential strategy to induce accommodation under clinical situation of pro-inflammation and pro-coagulation.
To cite this abstract in AMA style:Iwasaki K, Miwa Y, Haneda M, Kuzuya T, Ogawa H, Onishi A, Kobayashi T. AMPK Activator Promotes, but Complement and Thrombin Inhibit Anti-A/B Antibody-Induced Accommodation in Endothelial Cells [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/ampk-activator-promotes-but-complement-and-thrombin-inhibit-anti-ab-antibody-induced-accommodation-in-endothelial-cells/. Accessed April 7, 2020.
« Back to 2013 American Transplant Congress