CEACAM1 and molecular signaling pathways to expand the liver transplant donor pool
Samer Tohme, David A. Geller
Samer Tohme, David A. Geller
Published April 20, 2020
Citation Information: J Clin Invest. 2020;130(5):2192-2194. https://doi.org/10.1172/JCI136679.
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CEACAM1 and molecular signaling pathways to expand the liver transplant donor pool

Abstract

Organ shortage continues to limit the lives of patients who require liver transplantation. While extending criteria for liver organs provides a needed resource, tissue damage from prolonged ischemic injury can result in early allograft dysfunction and consequent rejection. In this issue of the JCI, Nakamura et al. used a mouse transplantation model with prolonged ex vivo cold storage to explore liver graft protection. The authors found that liver grafts with absent carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) exhibited increased ischemia-reperfusion injury inflammation and decreased function in wild-type recipients. The authors went on to correlate CEACAM1 levels with postreperfusion damage in human liver transplant recipients. Notably, this study identified a potential biomarker for liver transplant donor graft quality.

Authors

Samer Tohme, David A. Geller

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Figure 1

Model of the molecular mechanism for warm and cold IRI.

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Model of the molecular mechanism for warm and cold IRI. Cold stress decr...
Cold stress decreases CEACAM1 expression, which activates ASK/p38 and subsequent HMGB1 translocation from the nucleus to the cytoplasm to further block CEACAM1 and continue the inflammatory progression. Both cold and warm IRI activate the innate immune system, including liver Kupffer cells and neutrophils. The adaptive immune system is also triggered, eliciting complement activation and T cell activation. Involved inflammatory cells produce cytokines and chemokines, and generate ROS, further contributing to graft dysfunction.