Complement Activation in Liver Transplantation: Role of Donor Macrosteatosis and Implications in Delayed Graft Function

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2018 Jun 15

PMID 29899265

Citations 10

Authors

Kelley Nunez

Paul Thevenot

Abeer Alfadhli

Ari Cohen

Affiliations

Soon will be listed here.

Abstract

The complement system anchors the innate inflammatory response by triggering both cell-mediated and antibody-mediated immune responses against pathogens. The complement system also plays a critical role in sterile tissue injury by responding to damage-associated molecular patterns. The degree and duration of complement activation may be a critical variable controlling the balance between regenerative and destructive inflammation following sterile injury. Recent studies in kidney transplantation suggest that aberrant complement activation may play a significant role in delayed graft function following transplantation, confirming results obtained from rodent models of renal ischemia/reperfusion (I/R) injury. Deactivating the complement cascade through targeting anaphylatoxins (C3a/C5a) might be an effective clinical strategy to dampen reperfusion injury and reduce delayed graft function in liver transplantation. Targeting the complement cascade may be critical in donor livers with mild to moderate steatosis, where elevated lipid burden amplifies stress responses and increases hepatocyte turnover. Steatosis-driven complement activation in the donor liver may also have implications in rejection and thrombolytic complications following transplantation. This review focuses on the roles of complement activation in liver I/R injury, strategies to target complement activation in liver I/R, and potential opportunities to translate these strategies to transplanting donor livers with mild to moderate steatosis.

Citing Articles

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Immune response associated with ischemia and reperfusion injury during organ transplantation.

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Minimizing Ischemia Reperfusion Injury in Xenotransplantation.

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Effects of Gut Metabolites and Microbiota in Healthy and Marginal Livers Submitted to Surgery.

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