Phenotypical and Functional Polymorphism of Liver Resident Macrophages

Elchaninov, Andrey; Fatkhudinov, Timur; Vishnyakova, Polina; Lokhonina, Anastasia; Сухих, Г. Т.

doi:10.3390/cells8091032

Cited by 57 publications

(45 citation statements)

References 145 publications

(259 reference statements)

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“…These cells are highly malleable and can be altered according to changes in the microenvironment of the liver, both in morphology and function (Tacke and Zimmermann, 2014;Wynn and Vannella, 2016). In acute hepatic inflammatory injury, KCs release the pro-inflammatory cytokine inducible nitric oxide synthase (iNOS) through direct contact between cells and hepatocytes, and then release NO to effectively kill pathogens (Elchaninov et al, 2019). In order to limit the continuous stimulation of E. multilocularis and protect the stability of the liver environment, KCs secrete a large amount of profibrogenic cytokine transforming growth factor-β1 (TGF-β1), to promote the activation and proliferation of hepatic stellate cells (HSCs), a marker of liver fibrosis activation and leading to the occurrence and development of liver fibrosis (Lee and Friedman, 2011;Tosello-Trampont et al, 2011;Beljaars et al, 2014;Sica et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Kupffer Cells: Important Participant of Hepatic Alveolar Echinococcosis

Liu

Tian

Shan

et al. 2020

Front. Cell. Infect. Microbiol.

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Aims: Kupffer cells (KCs) are the liver-resident macrophages and play a leading role in the regulation of liver homeostasis in physiological conditions and in pathology. The study aims to investigate the anti-echinococcosis effect of KCs and the effects of hepatic stellate cells (HSCs) activation in the progression of liver fibrosis in hepatic alveolar echinococcosis (hepatic AE). Methods: Hematoxylin-eosin (H&E) and Masson staining were used to assess the pathological inflammatory changes and collagen deposition, respectively. Immunohistochemistry and qRT-PCR were used to detect the number of aggregates of KCs, the expression of cytokines and activation of HSCs. Results: In the close group, H&E staining showed that the normal lobular structure was destroyed and inflammatory infiltration around the lesion could be observed, and Masson staining showed that blue collagen fibers were clearly deposited near the portal area. IHC showed that KCs surface markers CD68 and CD163, cytokine iNOS and Arg-1 were positively expressed in the vicinity of inflammatory lesions. qRT-PCR indicated that TNF-α, IL-10, and TGF-β1 secreted by KCs were significantly higher than those in the distance group (P < 0.01). It is worth noticing that the expression levels of anti-inflammatory cytokines were slightly higher than that of pro-inflammatory cytokines. Both IHC and qRT-PCR results showed that HSCs activation markers, the expression of α-SMA and Desmin significantly increased. Conclusions: Our research indicates that KCs have immune-protective effect of anti-echinococcosis and promote liver fiber repair, and it also suggests that they have potential therapeutic value for patients with hepatic AE.

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Section: Introductionmentioning

confidence: 99%

Kupffer Cells: Important Participant of Hepatic Alveolar Echinococcosis

Liu

Tian

Shan

et al. 2020

Front. Cell. Infect. Microbiol.

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“…Kupffer cells (KCs), which account for 80-90% of all macrophages in mammalian organisms, play a key role in maintaining liver homeostasis in normal and pathological conditions, including liver IRI [4]. During the early stage of liver IRI, KCs are stimulated by damage-associated molecular patterns (DAMPs), high mobility group box 1 (HMGB1), and lipopolysaccharide (LPS) and then initiate excessive inflammation by releasing inflammatory cytokines and reactive oxygen species (ROS), which result in a positive feedback loop that increases the inflammatory cascade and leads to serious liver damage [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…During the early stage of liver IRI, KCs are stimulated by damage-associated molecular patterns (DAMPs), high mobility group box 1 (HMGB1), and lipopolysaccharide (LPS) and then initiate excessive inflammation by releasing inflammatory cytokines and reactive oxygen species (ROS), which result in a positive feedback loop that increases the inflammatory cascade and leads to serious liver damage [5,6]. Depending on the cell phenotype, macrophages can be divided into proinflammatory classically activated (M1) and anti-inflammatory alternatively activated (M2) macrophages [4]. M1 macrophages are characterized by the upregulation of proinflammatory cytokines, chemokines, and prostaglandins, such as IL-6, TNF-α, and IL-1β, to eliminate pathogens and facilitate the T helper type 1 ( 1) response.…”

Section: Introductionmentioning

confidence: 99%

IL‐4 Alleviates Ischaemia‐Reperfusion Injury by Inducing Kupffer Cells M2 Polarization via STAT6‐JMJD3 Pathway after Rat Liver Transplantation

Deng

Wang

et al. 2020

BioMed Research International

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Background. Liver ischaemia-reperfusion injury (IRI) remains a problem in liver transplantation. Interleukin-4 (IL-4) has been found to reduce liver IRI, but the exact mechanism remains unclear. Methods. Donor livers were infused with recombinant IL-4 or normal saline during cold storage, and the hepatocellular apoptosis and the inflammatory response were detected. The effect of IL-4 treatment on Kupffer cells (KCs) polarization and expression of the STAT6-JMJD3 pathway was evaluated in vivo and in vitro. KCs in donor livers were depleted by clodronate liposome treatment or JMJD3 was inhibited by GSK-J4 before liver transplantation to determine whether the protective effect of IL-4 treatment was dependent on KCs. Results. IL-4 treatment decreased sALT and sAST levels and alleviated hepatocellular apoptosis and inflammation at 6 h after liver transplantation. IL-4 treatment induced KCs alternatively activated (M2) polarization in vitro and in vivo, and the expression of STAT6 and JMJD3 was increased. JMJD3 knockdown abolished KCs M2 polarization and reduced the antiapoptotic and anti-inflammatory effects induced by IL-4 treatment in vitro. In addition, the protection of IL-4 treatment against IRI induced by liver transplantation was significantly reduced after the depletion of KCs or the inhibition of JMJD3 in donor livers. Conclusions. IL-4 treatment-induced KCs M2 polarization was dependent on the STAT6-JMJD3 pathway and protected liver grafts from IRI after liver transplantation.

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“…Resident macrophages of the liver, kupffer cells (KCs), represent a unique cell population. Most of the KCs belong to the self-sustaining macrophage cell population, whose origin is not in the bone marrow [3]. Blood monocytederived macrophages are a small fraction of macrophages in the liver.…”

Section: Introductionmentioning

confidence: 99%

“…KCs and monocyte-derived macrophages play different or crucial roles in the inflammatory response caused by persistent infection of the liver [7]. Different types of macrophages synthesize and secrete cytokines such as TNF-a, IL-1b, IL-6, IL-17, IL-4, IL-12, IL-18, IL-10 and IFN-γ will increase and fully participate in the immune response when they are stimulated [3,8,9]. M1 and M2 phenotypes are currently considered two extremes in the type of macrophage function.…”

Section: Introductionmentioning

confidence: 99%

Monocyte-derived Macrophages: the Supplements of Hepatic Macrophage in Echinococcus Multilocularis Infected Mice

Liu

et al. 2020

Preprint

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Background Alveolar echinococcosis (AE) is a potentially lethal zoonosis caused by the cestode Echinococcus multilocularis. The aim of this research is to investigate the dynamic changes of monocytes, macrophages and related cytokines in animal models of persistent infection of Echinococcus multilocularis, specifically exploring the possible immune changes in infection of Echinococcus multilocularis.Methods An infection model was established by intraperitoneal injection of a protoscolex suspension. The pathological changes of mice liver were observed by HE staining and the score scale of infection was established. The ratio of Ly6Chi and Ly6Clo Monocytes in peripheral blood of mice was detected by flow cytometry. The distribution and expression of CX3CL1, CX3CR1, iNOS, CD163 and CD11b in mouse liver were detected by immunohistochemistry. The mRNA expression levels of TNF-α and Arg1 in mouse liver were detected by qRT-PCR. The expression levels of INF-γ, IL-17, IL-4 and IL-10 in peripheral blood of mice were detected by ELISA.Results The results of HE staining showed that significant lesions appeared in the later stages of infection in the liver. The results of the infection degree score scale showed that the severity score value increased with the prolongation of the infection time. The results of flow cytometry showed that the proportion of Ly6Chi monocytes in the peripheral blood of the experimental group mice was decreased after a brief rise, Ly6Clo monocytes decreased first and then increased. The results of immunohistochemistry showed that the expression of CX3CL1, CX3CR1, CD11b, CD163 and iNOS in the mice liver of the experimental group was increased. The results of qRT-PCR showed that the expression level of TNF-α and Arg1 mRNA in the liver of the experimental group mice increased. The results of ELISA showed that the expression level of IFN-γ, IL-17, IL-4 and IL-10 increased with the duration of infection.Conclusions Monocytes as a supplement to hepatic macrophage, monocytes and kupffer cells (KCs) both participate in Th1 and Th2 immune responses of the body by differentiating into M1 or M2 at different stages of Echinococcus multilocularis infection.

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Phenotypical and Functional Polymorphism of Liver Resident Macrophages

Cited by 57 publications

References 145 publications

Kupffer Cells: Important Participant of Hepatic Alveolar Echinococcosis

Kupffer Cells: Important Participant of Hepatic Alveolar Echinococcosis

IL‐4 Alleviates Ischaemia‐Reperfusion Injury by Inducing Kupffer Cells M2 Polarization via STAT6‐JMJD3 Pathway after Rat Liver Transplantation

Monocyte-derived Macrophages: the Supplements of Hepatic Macrophage in Echinococcus Multilocularis Infected Mice

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