Macrophages and platelets in liver fibrosis and hepatocellular carcinoma
During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stag...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1277808/full |
| _version_ | 1827595601703862272 |
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| author | Martina Casari Dominik Siegl Carsten Deppermann Carsten Deppermann Detlef Schuppan Detlef Schuppan Detlef Schuppan |
| author_facet | Martina Casari Dominik Siegl Carsten Deppermann Carsten Deppermann Detlef Schuppan Detlef Schuppan Detlef Schuppan |
| author_sort | Martina Casari |
| collection | DOAJ |
| description | During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma. |
| first_indexed | 2024-03-09T02:55:52Z |
| format | Article |
| id | doaj.art-33a7d69edd854abfade7aaa448c73f3b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T02:55:52Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-33a7d69edd854abfade7aaa448c73f3b2023-12-05T05:01:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.12778081277808Macrophages and platelets in liver fibrosis and hepatocellular carcinomaMartina Casari0Dominik Siegl1Carsten Deppermann2Carsten Deppermann3Detlef Schuppan4Detlef Schuppan5Detlef Schuppan6Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, GermanyInstitute for Translational Immunology, University Medical Center of the Johannes Gutenberg-University, Mainz, GermanyCenter for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, GermanyResearch Center for Immune Therapy Forschungszentrum für Immuntherapie (FZI), University Medical Center of the Johannes Gutenberg-University, Mainz, GermanyInstitute for Translational Immunology, University Medical Center of the Johannes Gutenberg-University, Mainz, GermanyResearch Center for Immune Therapy Forschungszentrum für Immuntherapie (FZI), University Medical Center of the Johannes Gutenberg-University, Mainz, GermanyDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesDuring fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1277808/fullangiogenesiscollagenendothelial cellKupffer cellMMPmonocyte |
| spellingShingle | Martina Casari Dominik Siegl Carsten Deppermann Carsten Deppermann Detlef Schuppan Detlef Schuppan Detlef Schuppan Macrophages and platelets in liver fibrosis and hepatocellular carcinoma Frontiers in Immunology angiogenesis collagen endothelial cell Kupffer cell MMP monocyte |
| title | Macrophages and platelets in liver fibrosis and hepatocellular carcinoma |
| title_full | Macrophages and platelets in liver fibrosis and hepatocellular carcinoma |
| title_fullStr | Macrophages and platelets in liver fibrosis and hepatocellular carcinoma |
| title_full_unstemmed | Macrophages and platelets in liver fibrosis and hepatocellular carcinoma |
| title_short | Macrophages and platelets in liver fibrosis and hepatocellular carcinoma |
| title_sort | macrophages and platelets in liver fibrosis and hepatocellular carcinoma |
| topic | angiogenesis collagen endothelial cell Kupffer cell MMP monocyte |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1277808/full |
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