P594 PROMOTION OF LIVER INJURY AND FIBROSIS BY THE LIVER-DERIVED PLASMA PROTEIN HISTIDINE-RICH GLYCOPROTEIN IS BASED ON POLARIZING HEPATIC MACROPHAGES TOWARDS THE INFLAMMATORY M1 PHENOTYPE

2014 ◽  
Vol 60 (1) ◽  
pp. S267
Author(s):  
M. Bartneck ◽  
V. Fech ◽  
J. Ehling ◽  
X. Wei ◽  
K. Warzecha ◽  
...  
Keyword(s):  
Liver Injury ◽  
Plasma Protein ◽  
Hepatic Macrophages ◽  
M1 Phenotype

scholarly journals Caveolin-1 Deficiency Protects Mice Against Carbon Tetrachloride-Induced Acute Liver Injury Through Regulating Polarization of Hepatic Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziheng Yang ◽  
Jie Zhang ◽  
Yan Wang ◽  
Jing Lu ◽  
Quan Sun
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Liver Diseases ◽  
Acute Liver Injury ◽  
Mrna Levels ◽  
Alcoholic Fatty Liver ◽  
Caveolin 1 ◽  
Hepatic Macrophages ◽  
M1 Phenotype

Polarization of hepatic macrophages plays a crucial role in the injury and repair processes of acute and chronic liver diseases. However, the underlying molecular mechanisms remain elusive. Caveolin-1 (Cav1) is the structural protein of caveolae, the invaginations of the plasma membrane. It has distinct functions in regulating hepatitis, cirrhosis, and hepatocarcinogenesis. Given the increasing number of cases of liver cancer, nonalcoholic steatohepatitis, and non-alcoholic fatty liver disease worldwide, investigations on the role of Cav1 in liver diseases are warranted. In this study, we aimed to investigate the role of Cav1 in the pathogenesis of acute liver injury. Wild-type (WT) and Cav1 knockout (KO) mice (Cav1tm1Mls) were injected with carbon tetrachloride (CCl4). Cav1 KO mice showed significantly reduced degeneration, necrosis, and apoptosis of hepatocytes and decreased level of alanine transaminase (ALT) compared to WT mice. Moreover, Cav1 was required for the recruitment of hepatic macrophages. The analysis of the mRNA levels of CD86, tumor necrosis factor (TNF), and interleukin (IL)-6, as well as the protein expression of inducible nitric oxide synthase (iNOS), indicated that Cav1 deficiency inhibited the polarization of hepatic macrophages towards the M1 phenotype in the injured liver. Consistent with in vivo results, the expressions of CD86, TNF, IL-6, and iNOS were significantly downregulated in Cav1 KO macrophages. Also, fluorescence-activated cell sorting (FACS) analysis showed that the proportion of M1 macrophages was significantly decreased in the liver tissues obtained from Cav1 KO mice following CCl4 treatment. In summary, our results showed that Cav1 deficiency protected mice against CCl4-induced acute liver injury by regulating polarization of hepatic macrophages. We provided direct genetic evidence that Cav1 expressed in hepatic macrophages contributed to the pathogenesis of acute liver injury by regulating the polarization of hepatic macrophages towards the M1 phenotype. These findings suggest that Cav1 expressed in macrophages may represent a potential therapeutic target for acute liver injury.

scholarly journals Liver Injury and the Macrophage Issue: Molecular and Mechanistic Facts and Their Clinical Relevance

2021 ◽  
Vol 22 (14) ◽  
pp. 7249
Author(s):  
Siyer Roohani ◽  
Frank Tacke
Keyword(s):  
Bone Marrow ◽  
Liver Injury ◽  
Current Knowledge ◽  
Hepatocellular Cancer ◽  
Complete Recovery ◽  
Hepatic Macrophages ◽  
Liver Injuries ◽  
Microbial Products ◽  
Injured Liver

The liver is an essential immunological organ due to its gatekeeper position to bypassing antigens from the intestinal blood flow and microbial products from the intestinal commensals. The tissue-resident liver macrophages, termed Kupffer cells, represent key phagocytes that closely interact with local parenchymal, interstitial and other immunological cells in the liver to maintain homeostasis and tolerance against harmless antigens. Upon liver injury, the pool of hepatic macrophages expands dramatically by infiltrating bone marrow-/monocyte-derived macrophages. The interplay of the injured microenvironment and altered macrophage pool skews the subsequent course of liver injuries. It may range from complete recovery to chronic inflammation, fibrosis, cirrhosis and eventually hepatocellular cancer. This review summarizes current knowledge on the classification and role of hepatic macrophages in the healthy and injured liver.

Contribution of complement-stimulated hepatic macrophages and neutrophils to endotoxin-induced liver injury in rats

Hepatology ◽  
1994 ◽  
Vol 19 (4) ◽  
pp. 973-979 ◽  
Author(s):  
Hartmut Jaeschke ◽  
Anwar Farhood ◽  
C. Wayne Smith
Keyword(s):  
Liver Injury ◽  
Hepatic Macrophages

scholarly journals IL-1 receptor like 1 protects against alcoholic liver injury by limiting NF-κB activation in hepatic macrophages

2018 ◽  
Vol 68 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Meng Wang ◽  
Guannan Shen ◽  
Liangguo Xu ◽  
Xiaodong Liu ◽  
Jared M. Brown ◽  
...  
Keyword(s):  
Liver Injury ◽  
Alcoholic Liver Injury ◽  
Hepatic Macrophages

Potential role of hepatic macrophages in neutrophil-mediated liver injury in rats with sepsis

Hepatology ◽  
1993 ◽  
Vol 17 (6) ◽  
pp. 1086-1094 ◽  
Author(s):  
Fukashi Doi ◽  
Tomomochi Goya ◽  
Motomichi Torisu
Keyword(s):  
Liver Injury ◽  
Potential Role ◽  
Hepatic Macrophages

scholarly journals Liver injury changed the biological characters of serum small extracellular vesicles and reprogramed hepatic macrophages in mice

2021 ◽  
Author(s):  
Xiufang Lv ◽  
Jing Li ◽  
Li He ◽  
Li Cheng ◽  
Min Zhao ◽  
...  
Keyword(s):  
Liver Injury ◽  
Extracellular Vesicles ◽  
Liver Diseases ◽  
Human Liver ◽  
Mouse Liver ◽  
Liver Steatosis ◽  
Biological Significance ◽  
Circulating Mirnas ◽  
Hepatic Macrophages ◽  
Liver Macrophage

Abstract Background Serum small extracellular vesicles (sEVs) and their small RNA (sRNA) cargoes could be promising biomarkers for the diagnosis of liver injury. However, the dynamic changes of serum sEVs and their sRNA components during liver injury and the biological functions of these liver-injury-serum sEVs have not been well characterized. Methods To identify serum sEV biomarkers for liver injury, we established a carbon tetrachloride-induced mouse liver injury model to simulate acute liver injury (ALI), chronic liver injury (CLI) and recovery. Serum sEVs were obtained and characterized. Serum sEV sRNAs were profiled. Differentially expressed microRNAs (miRNA) were compared to mouse liver enriched miRNAs and previously reported circulating miRNAs that related to human liver diseases. The biological significance was evaluated by Ingenuity Pathway Analysis of altered sEV miRNAs, and conditional culture of ALI serum sEVs with primary hepatic macrophages. Results We found that both ALI and CLI changed the concentration and morphology of serum sEVs. The proportion of serum sEV miRNA increased upon liver injury, with the liver as the primary contributor. The altered serum sEV miRNAs based on mice's study were consistent with those human liver diseases-related circulating miRNAs. Serum sEV miRNA signatures for ALI and CLI, and a panel of miRNAs as common marker for liver injury, were established. The differential serum sEV miRNAs in ALI mainly contributed to liver steatosis and inflammation, while those in CLI primarily contributed to hepatocellular carcinoma and hyperplasia. ALI serum sEVs decreased both CD86 and CD206 expression in monocyte-derived macrophages, but increased CD206 expression in resident macrophages. Conclusion Serum sEVs in the different stages of liver injury carried different sRNA messages and contributed to diverse pathological processes. ALI serum sEVs might alleviate liver damage by depolarizing monocyte-derived macrophages and educating resident liver macrophage to M2 like cells.

scholarly journals Dual Role of Hepatic Macrophages in the Establishment of the Echinococcus multilocularis Metacestode in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Wang ◽  
Chuan-Shan Zhang ◽  
Bin-Bin Fang ◽  
Jiao Hou ◽  
Wen-Ding Li ◽  
...  
Keyword(s):  
Echinococcus Multilocularis ◽  
Liver Tissue ◽  
Parasite Burden ◽  
Dual Role ◽  
M2 Macrophages ◽  
Hepatic Macrophages ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
M2 Phenotype

Echinococcus multilocularis larvae, predominantly located in the liver, cause a tumor-like parasitic disease, alveolar echinococcosis (AE), that is characterized by increased infiltration of various immune cells, including macrophages, around the lesion that produces an “immunosuppressive” microenvironment, favoring its persistent infection. However, the role of hepatic macrophages in the host defense against E. multilocularis infection remains poorly defined. Using human liver tissues from patients with AE and a hepatic experimental mouse model of E. multilocularis, we investigated the phenotype and function of hepatic macrophages during the parasite infection. In the present study, we found that a large number of CD68+ macrophages accumulated around the metacestode lesion in the liver of human AE samples and that both S100A9+ proinflammatory (M1 phenotype) and CD163+ anti-inflammatory (M2 phenotype) macrophages were significantly higher in close liver tissue (CLT) than in distant liver tissue (DLT), whereas M2 macrophages represent the dominant macrophage population. Furthermore, E. multilocularis-infected mice exhibited a massive increase in macrophage (F4/80+) infiltration in the liver as early as day 5, and the infiltrated macrophages were mainly monocyte-derived macrophages (CD11bhi F4/80int MoMFs) that preferentially differentiated into the M1 phenotype (iNOS+) at the early stage of E. multilocularis infection and then polarized to anti-inflammatory macrophages of the M2 phenotype (CD206+) at the chronic stage of infection. We further showed that elimination of macrophages by treatment of mice with clodronate-liposomes before E. multilocularis infection impaired worm expulsion and was accompanied by a reduction in liver fibrosis, yielding a high parasite burden. These results suggest that hepatic macrophages may play a dual role in the establishment and development of E. multilocularis metacestodes in which early larvae clearance is promoted by M1 macrophages while persistent metacestode infection is favored by M2 macrophages.

scholarly journals ECK FISTULA LIVER SUBNORMAL IN PRODUCING HEMOGLOBIN AND PLASMA PROTEINS ON DIETS RICH IN LIVER AND IRON

1945 ◽  
Vol 81 (2) ◽  
pp. 171-191 ◽  
Author(s):  
G. H. Whipple ◽  
F. S. Robscheit-Robbins ◽  
W. B. Hawkins
Keyword(s):  
Liver Injury ◽  
Hepatic Artery ◽  
Plasma Protein ◽  
Functional Capacity ◽  
Liver Dysfunction ◽  
Plasma Proteins ◽  
Lethal Dose ◽  
Standard Diet ◽  
Histological Changes ◽  
Hemoglobin Production

The Eck fistula shunts the portal blood around the liver which receives its blood only by way of the hepatic artery. There are slight gross and histological changes in the Eck fistula liver of the dog. There is evidence at times of some functional abnormalities of the liver due to the Eck fistula but the dog can tolerate this fistula for 1 to 8 years and appear normal. Chloroform is tolerated by the Eck fistula dog, which may take twice a lethal dose for the control dog without evidence of significant liver injury. Acacia given by vein is deposited in the Eck fistula liver and impairs further its functional capacity to contribute to hemoglobin production. The stress of anemia brings out the fact that the anemic Eck fistula animal cannot utilize standard diet factors and iron as efficiently as the anemic non-Eck control dog. The output of new hemoglobin in some instances may drop to one-fourth of normal. When hypoproteinemia alone or combined with anemia is produced in the Eck fistula dog, we observe at times very low production of plasma protein—seven a drop to one-tenth of normal. This interrelation of liver abnormality, liver dysfunction, and lessened plasma protein and hemoglobin production is significant. It is generally accepted that the liver is concerned with the production of several plasma proteins—fibrinogen, prothrombin, and albumin. The experiments above indicate that the liver is concerned directly or indirectly with the production of new hemoglobin. Our belief is that the liver contributes to the fabrication of hemoglobin by means of the mobile plasma proteins which to a large extent derive from the liver.

scholarly journals ARRB1 suppresses the activation of hepatic macrophages via modulating endoplasmic reticulum stress in lipopolysaccharide-induced acute liver injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yiming Lei ◽  
Sizhe Wan ◽  
Huiling Liu ◽  
Haoxiong Zhou ◽  
Lingjun Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Liver Injury ◽  
Er Stress ◽  
Cell Lines ◽  
Macrophage Activation ◽  
Acute Liver Injury ◽  
Vital Event ◽  
Hepatic Macrophages ◽  
Liver Macrophage ◽  
Hepatic Macrophage

AbstractAcute liver injury (ALI) caused by multiple inflammatory responses is a monocyte-/macrophage-mediated liver injury that is associated with high morbidity and mortality. Liver macrophage activation is a vital event that triggers ALI. However, the mechanism of liver macrophage activation has not been fully elucidated. This study examined the role of β-arrestin1 (ARRB1) in wild-type (WT) and ARRB1-knockout (ARRB1-KO) mouse models of ALI induced by lipopolysaccharide (LPS), and ARRB1-KO mice exhibited more severe inflammatory injury and liver macrophage activation compared to WT mice. We found that LPS treatment reduced the expression level of ARRB1 in Raw264.7 and THP-1 cell lines, and mouse primary hepatic macrophages. Overexpression of ARRB1 in Raw264.7 and THP-1 cell lines significantly attenuated LPS-induced liver macrophage activation, such as transformation in cell morphology and enhanced expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), while downregulation of ARRB1 by small interfering RNA and ARRB1 deficiency in primary hepatic macrophages both aggravated macrophage activation. Moreover, overexpression of ARRB1 suppressed LPS-induced endoplasmic reticulum (ER) stress in liver macrophages, and inhibition of ER stress impeded excessive hepatic macrophage activation induced by downregulation of ARRB1. Our data demonstrate that ARRB1 relieves LPS-induced ALI through the ER stress pathway to regulate hepatic macrophage activation and that ARRB1 may be a potential therapeutic target for ALI.

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