Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Institute for Translational Immunology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Front Immunol. 2023 Dec 5;14:1277808. doi: 10.3389/fimmu.2023.1277808. eCollection 2023.
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.
在纤维化过程中，（肌）成纤维细胞会沉积大量细胞外基质蛋白，从而取代健康的功能性组织。在肝纤维化中，这会导致肝细胞功能丧失、门静脉高压、静脉曲张出血以及增加感染易感性。在早期，肝纤维化是一个动态和可逆的过程，然而，从肝硬化阶段开始，就会向肝细胞癌显著进展。肝固有巨噬细胞（库普弗细胞）和单核细胞衍生的巨噬细胞都是纤维化进展的重要驱动因素，但一旦慢性炎症的触发因素消除，它们也可以诱导其逆转。在肝癌中，它们被吸引到肿瘤部位成为肿瘤相关巨噬细胞（TAMs），向 M2-抗炎/促肿瘤表型极化。除了在血栓形成和止血中的作用外，血小板还可以通过分泌促纤维化因子和调节先天免疫反应来刺激纤维化和肿瘤的发展，例如，通过与单核细胞和巨噬细胞相互作用。在这里，我们回顾了关于巨噬细胞和血小板及其在肝纤维化和肝细胞癌中的相互作用的最新文献。
