In the same study, knockout of miR-155 also alleviated the inflammation and steatosis triggered by chronic alcohol ingestion (37). Macrophage Function and Location . DerivedFrom doi: 10.1053/j.gastro.2009.09.009, 79. (2000) 106:867–72. SourceModified (2019) 71:1086–98. (2007) 82:479–87. pdfaid XMP08 Spec: An ordered array of plate names that are needed to print the document (including any in contained documents). The removal of dying cells is, to a greater extent, handled by fixed macrophages, which will stay at strategic locations such as the lungs, liver, neural tissue, bone, spleen and connective tissue, ingesting foreign materials such as pathogens and recruiting additional macrophages if needed. Given the overwhelming success of the first edition, which appeared in 2001, and fast development in the different fields of cancer research, it has been decided to publish a second fully revised and expanded edition. Springer Nature ORCID Schema (2016) 20:445–56. However, this theory has been challenged by a recent study that revealed a common progenitor for tissue-resident macrophages, called premacrophages, which were generated early in development and had colonized the whole embryo from embryonic day 9.5. A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. To examine the induction of liver inflammation, we compared 2 typical conditions—the steady condition versus the inflammatory condition—using an acute T cell-mediated . A major function of macrophages in host defense is to ingest and kill microbes. Increased sCD163 is associated with dis-ease severity in several liver diseases [10-12] and with prognosis in patients with liver cirrhosis and acute- In an animal model, ethanol feeding promoted the differentiation of Ly6Chi monocytes into tissue-damaging pro-inflammatory macrophages (43). Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. This book provides readers with an up-to-date and comprehensive view on the resolution of inflammation and on new developments in this area, including pro-resolution mediators, apoptosis, macrophage clearance of apoptotic cells, possible ... (1997) 51:944–50. These macrophages are likely to contribute to hepatic inflammation and damage in distinct liver diseases. J Leukoc Biol. specific marker of monocyte/macrophage activation. (2011) 56:1057–64. Taken together, interaction between T cells and KCs hinders antitumor response by promoting T-cell exhaustion in HCC. resident macrophages, leading to distinct epigenetic profiles, transcriptional programmes and, ultimately, different functions. TNF) observed . (2017) 17:306–21. Macrophage activation and polarization: nomenclature and experimental guidelines. Tea Lund Laursen One connection between KCs and NASH is the presence of hepatic stellate cells (HSCs). Blood. Click again to see term . Nat Immunol. authorInfo found that ethanol exposure stimulated hepatocytes to produce considerably more CD40L-containing extracellular vesicles in a caspase-3-dependent manner, ultimately triggering macrophage activation and production of MCP-1, TNF-α, and ROS (39) (Figure 1A). endstream In vitro stimulation with HBsAg and HBeAg promoted primary human non-parenchymal liver cells to produce IL-6, IL-8, TNF-α, and IL-1β via the NF-κB pathway (67, 68). (2014) 6:1336–45. doi: 10.1016/j.cmet.2008.04.003. Seq Text Notably, during alcohol exposure, KCs are a major source of ROS, which is essential for LPS sensitization (40) and inflammatory cytokine production (41) (Figure 1A). internal %PDF-1.4 Found insideIt is the wish of all multidisciplinary experts who gather prominent author's panel of this volume to incorporate latest medical reports and compel limits of current understanding for better tissue regeneration, limb salvage, and improved ... Lung macrophages stained with Wright-Giemsa Macrophages originate from blood monocytes KCs also express a wide range of pattern recognition receptors (PRRs), including toll-like receptors (TLRs) (8), nucleotide oligomerization (NOD)-like receptors (9), and retinoic acid-inducible gene I (RIG-I)-like receptors (10). (2014) 10:e1004032. Recent studies have found that hepatic macrophages have different functions in different stages of experimental liver fibrosis. Oakley F, Meso M, Iredale JP, Green K, Marek CJ, Zhou X, et al. 10.1186/s13023-018-0910-7 Trapped (2019) 16:145–59. what are some functions of macrophages? Macrophages Function. Hepatic macrophage (Kupffer cell) hyperplasia is often described in Wilson's disease (WD). Phagocytosis of bacteria, viruses, and other foreign particles is the most important function of macrophages. Elsegood CL, Chan CW, Degli-Esposti MA, Wikstrom ME, Domenichini A, Lazarus K, et al. Several strategies have been employed to specifically target hepatic macrophages in different liver diseases (Table 1). Exp Biol Med. One hypothesis for these phenomena is that the phenotype of the hepatic macrophages may be shaped by HBV/HCV as the infection progresses. doi: 10.1016/j.immuni.2014.06.008, 106. Cell Metab. Exposure by saturated fatty acid causes hepatocyte lipotoxicity that then promotes pro-inflammatory macrophage differentiation, whereas stimulation by unsaturated fatty acids activates PPARδ to enhance anti-inflammatory differentiation in NASH (Figure 1B) (52, 59). doi: 10.1016/j.dld.2011.11.005, 77. Gastroenterology. Liver injury may trigger hepatic recruitment of peritoneal macrophages and monocyte-derived macrophages. Wu K, Kryczek I, Chen L, Zou W, Welling TH. Recent experiments found that KCs and recruited macrophages may play different roles in the development of liver disease. Karakucuk I, Dilly SA, Maxwell JD. (2019). To sum up, during HCC progression, macrophages and MDSCs are recruited to the liver via the CCL2/CCR2 axis; these cells have been shown to promote tumor proliferation and metastasis. doi: 10.1002/hep4.1356, 25. J Hepatol. Moreover, the triggering receptor expressed on myeloid cells-1 (TREM-1) is an activating receptor that is widely expressed on monocytes, macrophages, and neutrophils (93). Moreover, there is also intertwined regulation of macrophage functions from different compartments such as circulation, bone marrow, AT, gut and liver. In the murine liver, there are two major macrophage populations, namely resident Kupffer cells (resKCs) with phagocytic activity and recruited macrophages (recMφs) with cytokine-producing capacity. Wan S, Kuo N, Kryczek I, Zou W, Welling TH. (2012) 72:3977. doi: 10.1158/0008-5472.CAN-12-0938, 95. (2007) 27:549–59. Conformance level of PDF/X standard http://springernature.com/ns/xmpExtensions/2.0/ 33. URI (2011) 11:762–74. Macrophages play important roles in the immune system's initial response to bacteria, viruses and wounds. Self-renewing peritoneal macrophages have been shown to migrate to the liver in response to sterile injury (23). Text Nebbia G, Peppa D, Schurich A, Khanna P, Singh HD, Cheng Y, et al. The bone-marrow-derived macrophages are CD11b+, F4/80+, CCR2+, and CX3CR1+. (2006) 12:7413–20. doi: 10.1164/rccm.200704-641OC, 94. J Hepatol. Skeletal muscle. Your liver is the largest organ inside your body, weighing about 1.4 kg (3 pounds) in an average adult. CD11b+Ly6Chi subsets can infiltrate into the liver during inflammation (20), whereas the Ly6Clow monocytes serve as sentinels to scavenge microparticles and cell debris in the capillaries (21). Skeletal muscle. Hellerbrand C, Stefanovic B, Giordano F, Burchardt ER, Brenner DA. Oncogene. Adaptive immunity suppresses formation and progression of diethylnitrosamine-induced liver cancer. Specifies the types of series editor information: name and ORCID of a series editor. Gadolinium chloride blocks alcohol-dependent liver toxicity in rats treated chronically with intragastric alcohol despite the induction of CYP2E1. The Liver. PDF/A ID Schema Pathogenesis of alcoholic liver disease. To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. The human immune system is responsible for identifying, destroying, and removing all foreign substances from the body. Part of PDF/A standard 7a) and express a distinct tissue-resident macrophage phenotype, downregulating CR3 and expressing CRIg, a tissue-specific complement receptor, as well as a liver-specific lectin for alpha-galactosyl ceramide , reflecting their function in innate recognition and . Verma VK, Li H, Wang R, Hirsova P, Mushref M, Liu Y, et al. (2011) 10:2. doi: 10.1186/1476-5926-10-2, PubMed Abstract | CrossRef Full Text | Google Scholar. doi: 10.1016/j.jhep.2014.04.026, 67. PLoS ONE. (2016) 13:316–27. Cancer Res. XMP Paged-Text Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice. The Ly6Chi monocyte can differentiate into pro-inflammatory and anti-inflammatory macrophages during ALD, and the ratio of these two populations may mediate ALD development. During the early phase of infection, hepatic macrophages are dominated by pro-inflammatory subsets that inhibit virus development by producing cytokines with antiviral activity. About 20% of patients who suffer from non-alcoholic fatty liver disease will develop NASH, which is defined by the existence of progressive fibrosis and steatosis with inflammation, ultimately leading to HCC and cirrhosis. J Hepatol. In addition, IL-1β and TNF-α production by stimulated KCs was required to maintain HSC survival via the NF-κB pathway (48) (Figure 1B). doi: 10.1189/jlb.1A0314-170R, 58. In the same study, Trem1 deficiency diminished IL-1β, IL-6, TNF, CCL2, and CXCL10 release by KCs and suppressed HCC growth (94). Macrophages, the most abundant liver immune cells, play a critical role in maintaining hepatic homeostasis and the underlying mechanisms of liver diseases. In contrast, the chronic hepatitis infection environment suppresses hepatic macrophages polarizing toward the pro-inflammatory phenotype and pushes cells toward the immunoregulation phenotype. Editor information: contains the name of each editor and his/her ORCID identifier. J Virol. A majority of macrophages are stationed at strategic points where microbial invasion or accumulation of foreign particles is likely to occur. (2018) 67:1754–67. 1 0 obj Additionally, the spleen is thought to be a reservoir for inflammatory monocytes, which infiltrate the liver and differentiate into hepatic macrophages during liver injury (106). doi: 10.1126/science.1219179, 19. Gives the ORCID of an author. (2019) 3:730–43. Wang M, You Q, Lor K, Chen F, Gao B, Ju C. Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice. Mitochondrial DNA from hepatocytes of high-fat diet (HFD)-fed mice activates KCs and promotes cytokine release, steatosis, and inflammation. Kupffer cells contain the largest amount of tissue-resident macrophages in the body. (2011) 332:1284–8. Isorce N, Testoni B, Locatelli M, Fresquet J, Rivoire M, Luangsay S, et al. Recent studies showed that a small non-coding RNA, termed microRNA (miRNA), is involved in regulating macrophage infiltration, activation, and ALD progression (Figure 1A). Wang Y, van der Tuin S, Tjeerdema N, van Dam AD, Rensen SS, Hendrikx T, et al. Some studies found that there are different types of hepatic macrophages in the liver, although others have suggested that hepatic macrophages could switch to different . Lipid-induced signaling causes release of inflammatory extracellular vesicles from hepatocytes. Increases in intrahepatic CD68 positive cells, MAC387 positive cells, and proinflammatory cytokines (particularly interleukin 18) in chronic hepatitis C infection. Liver immunobiology. Thomas Barwick / Getty Images. Furthermore, the supernatant from differentiated pro-inflammatory macrophages contains reasonable amounts of IL-1β and IL-6, which inhibit the progression of HBV by decreasing levels of hepatitis B surface antigen (HBsAg) and hepatitis B early antigen (HBeAg) (65). doi: 10.1016/j.ccell.2016.09.003, 98. (2014) 61:660–71. HSC-derived macrophages differentiate from circulating myeloid precursor cells from the bone marrow; this process is mediated by colony-stimulating factor (CSF)-1 (17, 18). KCs, self-renewing tissue-resident phagocytes, are located in the liver sinusoids. sn Together, these chemokines recruit natural killer (NK), NKT, dendritic cells (DC), and CD4+ T cells to infected sites to accelerate infection clearance (74, 75). Am J Respir Crit Care Med. 2018A030313019); National Natural Science Foundation of China (Grant No. Additionally, KCs are involved in controlling the iron (5), cholesterol (6), and bilirubin (7) balance of the blood. MicroRNA 181b-3p and its target importin α5 regulate toll-like receptor 4 signaling in Kupffer cells and liver injury in mice in response to ethanol. (2009) 69:8067–75. Kupffer cell sensitization by alcohol involves increased permeability to gut-derived endotoxin. J Clin Invest. pdf CSF1R inhibition affects function and survival of resident and interstitial macrophages. Text Science. Schnabl B, Brenner DA. The role of recruited macrophages in HCC development is highlighted by the importance of the CCL2/CCR2 signaling axis, which is crucial for Ly6Chi monocyte recruitment to inflammatory sites (95). internal Bag Font orcid PLoS Pathog. internal Clin Transl Immunol. An HFD augments the infiltration of bone-marrow-derived monocytes into the liver and further differentiates them into protective anti-inflammatory macrophages. A recent study suggested an extension to the M1–M2 model by showing that, other than M1 and M2 macrophages, human macrophages can be polarized into distinct phenotypes in response to various stimuli (103). , Bull. WHO, 1972, 46: 845-852). The paradigm of the MPS has the advantage of being much more consistent than the Reticuloendothelial System (RES) (L. Aschoff, Ergebn. Inn. Med. (2003) 228:882–90. doi: 10.1124/mol.51.6.944, 30. The proinflammatory myeloid cell receptor TREM-1 controls Kupffer cell activation and development of hepatocellular carcinoma. Impact Factor 7.561 | CiteScore 8.1More on impact ›, Macrophages in Liver Disease It has been documented that the cannabinoid receptor 2 (CB2) expressed on KCs protects mice from ALD via an autophagy pathway (Figure 1A). This book provides a comprehensive overview of the diagnosis and management of Non-alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatis (NASH). doi: 10.1016/S0168-8278(99)80010-5, 47. Subsequently, inflammatory monocytes accumulate in the liver via . doi: 10.1002/hep.29477, 59. Sinusoids. In a mouse model of NASH, fibrosis, inflammation, and steatosis were diminished in the livers of STING-deficient mice (50). Alcohol Clin Exp Res. doi: 10.1158/0008-5472.CAN-11-1792, 102. Hepatology. Circulating monocytes are classified into CD11b+Ly6Chi (20) and CD11b+Ly6Clow (21) in mice. Thomas Barwick / Getty Images. (2016) 150:1769–77. They have phagocytosis capacity and release all kinds of cytokines, chemokines, and soluble biological mediators. 2018-09-21T16:37:01+02:00 The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. doi: 10.1053/j.gastro.2016.02.066, 45. endobj Macrophages assist in the development of blood vessel networks in the ovary, which is vital for the production of the . (2013) 58:1461–73. Brempelis KJ, Crispe IN. Hepatic macrophages form highly heterogeneous populations, and several markers have been used to distinguish between KCs and recruited macrophages. Tap again to see term . Mass E, Ballesteros I, Farlik M, Halbritter F, Gunther P, Crozet L, et al. KCs have been demonstrated to function as incomplete antigen-presenting cells (APCs) to induce T-cell tolerance (89). Recent research has shown that mitochondrial DNA from hepatocytes of high-fat diet (HFD)-fed mice activates KCs and induces steatosis and inflammation via the stimulator of IFN genes (STING) pathway (50) (Figure 1B). In comparison with that in controls, collagen-α1(I) messenger RNA (mRNA) was substantially increased in carbon tetrachloride (CCl4)-treated mice, and this increase was abolished in TGF-β1-knockout mice (47). converted to PDF/A-2b doi: 10.1016/j.jhep.2009.12.015, 69. internal Similarly, high galectin-9 expression is seen on the KCs of patients with chronic HBV infections (79). PLoS Pathog. Under hemolytic stress, these antiinflammatory erythrophagocytes become the predominant macrophage population leading to a pronounced attenuation in 2 models of inflammatory liver disease. You Q, Cheng L, Kedl RM, Ju C. Mechanism of T cell tolerance induction by murine hepatic Kupffer cells. (2016) 304:110–20. xmpTPg Yeung OW, Lo CM, Ling CC, Qi X, Geng W, Li CX, et al. YG, XH, and XS contributed to manuscript revision and read and approved the submitted version. In ethanol-fed rats, the overexpression of miR181b-3p inhibited importin α5 expression and suppressed LPS-induced TNF-α expression in KCs (35). But beyond that, each tissue macrophage also has specialized functions, tuned to the needs of that particular tissue. Moreover, phagocytosis of apoptotic hepatocytes allows Ly6Chi monocytes/macrophages to switch to Ly6Clow monocytes/macrophages, which then differentiate into tissue-protective macrophages (43) (Figure 1A). Gastroenterology. Alcohol stimulates macrophage activation through caspase-dependent hepatocyte derived release of CD40L containing extracellular vesicles. Gives the name of a series editor. doi: 10.1002/hep.25777, 93. Text doi: 10.1016/j.cell.2013.03.010, 22. The liver is immediately downstream of the pancreas and clears 40-80% of the insulin [[324, 325]]. doi: 10.1084/jem.20082173, 91. Guo Q, Furuta K, Lucien F, Gutierrez Sanchez LH, Hirsova P, Krishnan A, et al. Activated KCs, characterized by the upregulation of CD33 and CD163, accumulate in the portal tract during chronic HBV/HCV infection, highlighting the importance of these cells in fighting viral hepatitis (60, 61). The text presents comprehensive coverage of their already established role in hepatic fibrosis along with the newer emerging evidence for stellate cell participation in the liver cell (hepatocyte) survival and regeneration, hepatic ... J Leukoc Biol. Cell Mol Immunol. This study was performed to clarify the functional differences between these two populations, focusing on their susceptibility to radiation and response to stimulation via liver X receptors (LXRs . (2017) 66:746–57. Lesokhin AM, Hohl TM, Kitano S, Cortez C, Hirschhorn-Cymerman D, Avogadri F, et al. (2003) 10:159–67. doi: 10.1128/JVI.00996-08, 74. Integrin β1-enriched extracellular vesicles mediate monocyte adhesion and promote liver inflammation in murine NASH. The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis. 2015B050501002). Hepatol Commun. Comp Hepatol. Keywords provided by University of Aarhus: Procedure: Functional Hepatic Nitrogen Clearance (FHNC), Procedure: Galactose Elimination Capacity (GEC). Sasaki R, Devhare PB, Steele R, Ray R, Ray RB. Macrophages are found in almost every tissue in the body and perform a number of functions outside of immunity. Macrophages are found in almost every tissue in the body and perform a number of functions outside of immunity. Necrosis of pericentral hepatocytes is a typical histological feature of injured tissue in the CCl 4-induced acute liver injury model.We observed severely destroyed pericentral zones at 48 h after CCl 4 . Hepatology. uuid:18c331bb-1951-47e3-9d0d-980e3a8bc9f5 Tan AT, Koh S, Goh W, Zhe HY, Gehring AJ, Lim SG, et al. doi: 10.1007/978-3-540-33397-5_2, 75. Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Please remove one or more studies before adding more. Click card to see definition . Wilson disease,Macrophages,Liver,Metabolic liver function,sCD163 YG was supported by the Natural Science Foundation of Guangdong Province (Grant No. Studies have found that KCs suppress antitumor activity by inducing T-cell tolerance and dysfunction in an HCC setting. Hepatic macrophages are a remarkably heterogeneous population consisting of self-renewing tissue-resident phagocytes, termed Kupffer cells (KCs), and recruited macrophages derived from peritoneal cavity as well as the bone marrow. Plasma cholesteryl ester transfer protein is predominantly derived from Kupffer cells. A major function of macrophages in host defense is to ingest and kill microbes. 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