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The Role of Complement in Liver Injury, Regeneration, and Transplantation

The liver is both an immunologically complex and a privileged organ. The innate immune system is a central player, in which the complement system emerges as a pivotal part of liver homeostasis, immune responses, and crosstalk with other effector systems in both innate and adaptive immunity. The live...

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Autores principales: Thorgersen, Ebbe Billmann, Barratt‐Due, Andreas, Haugaa, Håkon, Harboe, Morten, Pischke, Søren Erik, Nilsson, Per H., Mollnes, Tom Eirik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771474/
https://www.ncbi.nlm.nih.gov/pubmed/30653682
http://dx.doi.org/10.1002/hep.30508
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author Thorgersen, Ebbe Billmann
Barratt‐Due, Andreas
Haugaa, Håkon
Harboe, Morten
Pischke, Søren Erik
Nilsson, Per H.
Mollnes, Tom Eirik
author_facet Thorgersen, Ebbe Billmann
Barratt‐Due, Andreas
Haugaa, Håkon
Harboe, Morten
Pischke, Søren Erik
Nilsson, Per H.
Mollnes, Tom Eirik
author_sort Thorgersen, Ebbe Billmann
collection PubMed
description The liver is both an immunologically complex and a privileged organ. The innate immune system is a central player, in which the complement system emerges as a pivotal part of liver homeostasis, immune responses, and crosstalk with other effector systems in both innate and adaptive immunity. The liver produces the majority of the complement proteins and is the home of important immune cells such as Kupffer cells. Liver immune responses are delicately tuned between tolerance to many antigens flowing in from the alimentary tract, a tolerance that likely makes the liver less prone to rejection than other solid organ transplants, and reaction to local injury, systemic inflammation, and regeneration. Notably, complement is a double‐edged sword as activation is detrimental by inducing inflammatory tissue damage in, for example, ischemia–reperfusion injury and transplant rejection yet is beneficial for liver tissue regeneration. Therapeutic complement inhibition is rapidly developing for routine clinical treatment of several diseases. In the liver, targeted inhibition of damaged tissue may be a rational and promising approach to avoid further tissue destruction and simultaneously preserve beneficial effects of complement in areas of proliferation. Here, we argue that complement is a key system to manipulate in the liver in several clinical settings, including liver injury and regeneration after major surgery and preservation of the organ during transplantation.
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spelling pubmed-67714742019-10-03 The Role of Complement in Liver Injury, Regeneration, and Transplantation Thorgersen, Ebbe Billmann Barratt‐Due, Andreas Haugaa, Håkon Harboe, Morten Pischke, Søren Erik Nilsson, Per H. Mollnes, Tom Eirik Hepatology Reviews The liver is both an immunologically complex and a privileged organ. The innate immune system is a central player, in which the complement system emerges as a pivotal part of liver homeostasis, immune responses, and crosstalk with other effector systems in both innate and adaptive immunity. The liver produces the majority of the complement proteins and is the home of important immune cells such as Kupffer cells. Liver immune responses are delicately tuned between tolerance to many antigens flowing in from the alimentary tract, a tolerance that likely makes the liver less prone to rejection than other solid organ transplants, and reaction to local injury, systemic inflammation, and regeneration. Notably, complement is a double‐edged sword as activation is detrimental by inducing inflammatory tissue damage in, for example, ischemia–reperfusion injury and transplant rejection yet is beneficial for liver tissue regeneration. Therapeutic complement inhibition is rapidly developing for routine clinical treatment of several diseases. In the liver, targeted inhibition of damaged tissue may be a rational and promising approach to avoid further tissue destruction and simultaneously preserve beneficial effects of complement in areas of proliferation. Here, we argue that complement is a key system to manipulate in the liver in several clinical settings, including liver injury and regeneration after major surgery and preservation of the organ during transplantation. John Wiley and Sons Inc. 2019-07-15 2019-08 /pmc/articles/PMC6771474/ /pubmed/30653682 http://dx.doi.org/10.1002/hep.30508 Text en © 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Reviews
Thorgersen, Ebbe Billmann
Barratt‐Due, Andreas
Haugaa, Håkon
Harboe, Morten
Pischke, Søren Erik
Nilsson, Per H.
Mollnes, Tom Eirik
The Role of Complement in Liver Injury, Regeneration, and Transplantation
title The Role of Complement in Liver Injury, Regeneration, and Transplantation
title_full The Role of Complement in Liver Injury, Regeneration, and Transplantation
title_fullStr The Role of Complement in Liver Injury, Regeneration, and Transplantation
title_full_unstemmed The Role of Complement in Liver Injury, Regeneration, and Transplantation
title_short The Role of Complement in Liver Injury, Regeneration, and Transplantation
title_sort role of complement in liver injury, regeneration, and transplantation
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771474/
https://www.ncbi.nlm.nih.gov/pubmed/30653682
http://dx.doi.org/10.1002/hep.30508
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