Kupffer cell activation. Medical search. Frequent questions

Kupffer cells, also known as stellate macrophages and Kupffer-Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. (wikipedia.org)
Kupffer cells comprise the largest population of tissue-resident macrophages in the body. (wikipedia.org)
Development of an initial population of Kupffer cells begins in the embryonic yolk sac where precursor cells differentiate into fetal macrophages. (wikipedia.org)
Unlike other tissue macrophages, which must be continually renewed by circulating monocytes, these monocyte-derived Kupffer cells are capable of self-renewal once a population is established. (wikipedia.org)
Kupffer cells have a proliferative capacity, allowing for cell populations to replenish themselves: this is in complete contrast to monocyte-derived macrophages that have no proliferative potential. (wikipedia.org)
AML12 cells had no such response, suggesting that the accumulation of autophagosomes caused by CDs may be specific to macrophages. (biomedcentral.com)
Moreover, the liver contains the mononuclear phagocyte system (MPS) with rich population of macrophages (Kupffer cells) that take up nanoparticles. (biomedcentral.com)
Hepatic macrophages known as Kupffer cells (KUP5 cells or KCs), play a key role in immune defense, participating in phagocytosis and submitting immune response signals in the early stages of chemical exposure. (biomedcentral.com)
CD163 antigens in macrophages of heart (A), liver (Kupffer cells) (B), spleen (C), and testicle (D). Original magnification ×20. (cdc.gov)
Kupffer cells, hepatic stellate cells and sinusoidal endothelium) and infiltrating leukocytes (e.g., monocytes, monocyte-derived macrophages, neutrophils and lymphocytes). (mdpi.com)
A review on the relationship of mast cells and macrophages in breast cancer - Can herbs or natural products facilitate their anti-tumor effects? (spandidos-publications.com)
Background: Hepatic fat accumulation modulates innate immunity causing recruitment of bone marrow derived macrophages/activation of Kupffer cells, resulting in inflammatory changes associated with the development of insulin resistance and NASH. (diabetesjournals.org)
Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. (wanfangdata.com.cn)
It is reported that IL-18 is produced from Kupffer cells, activated macrophages, keratinocytes, intestinal epithelial cells, osteoblasts, adrenal cortex cells and murine diencephalon. (rndsystems.com)
IFN-gamma activates macrophages, enhances NK activity and B cell maturation, proliferation and Ig secretion, induces MHC class I and II antigens, and inhibits osteoclast activation. (rndsystems.com)
including hepatic stellate cells, liver adipocytes, liver resident macrophages kupffer cells, endothelial cells and infiltrating immune cells. (edu.au)
Mutations in the gene encoding CSF1R have been associated with a predisposition to myeloid malignancy.Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. (thermofisher.com)
Furthermore, PNS activation increases the expression of IL-6 in macrophages by acting on muscarinic Ach receptors (mAChRs). (e-cmh.org)
In this chapter, we have summarized results of our studies that suggest a contributing role for surface Fenton-reactive metal ion in particulate-mediated inflammatory activation of macrophages and the consequent endothelial inflammatory activation by macrophage-elaborated soluble factors. (cdc.gov)
Furthermore, clarified culture supernatants recovered from C- Fe-treated macrophages raise vascular endothelial cells to an activated state as indicated by the induction of endothelial- leukocyte adhesion molecules ICAM-1, VCAM-1, and E-selectin. (cdc.gov)

Their role in fibrosis is well established as they are one of the main sources of TGFβ1 production, which leads to the transformation of stellate cells into myofibroblasts. (wanfangdata.com.cn)
After a comprehensive review of all the current in vitro models of the liver we hypothesised that a liver organoid cell culture model co-cultured with myofibroblast like hepatic stellate cells can model liver injury. (edu.au)
We established a 3D liver organoid cell culture model from primary mouse tissue and characterised the capacity of these organoids to model liver characteristics in vitro and used this model to define the interactions between organoid hepatocytes and hepatic stellate cells in a co-culture trans-well system. (edu.au)
Hepatic stellate cell dependent decreases in organoid viability and organoid dependent increases in hepatic stellate cell viability were observed, as well as Halofuginone dependent decreases in hepatic stellate cell viability were also observed. (edu.au)
Markers characteristic of liver injury and fibrosis, such as Actn1 and Lamb3 were upregulated in hepatic stellate cells, although collagen expression was downregulated in these cells. (edu.au)
Transcriptional profiling revealed a tumour necrosis factor-α mediated apoptotic response in organoids and an inflammatory response in both the organoids and hepatic stellate cells. (edu.au)
Activation of the hepatic perivascular stellate cells (Ito cells, which store fat) initiates fibrosis. (msdmanuals.com)
Thus, stellate cell activation results in abnormal extracellular matrix, both in quantity and composition. (msdmanuals.com)
This was due to hepatic ischemia, endothelial injury, and activation of neutrophils, Kupffer cells, and hepatic stellate cells. (elsevierpure.com)
Hepatic stellate cells (HSC) have recently been identified as liver-resident mesenchymal stem cells and are thought to contribute to liver repair and fibrogenesis [ 1 ]. (biomedcentral.com)
The aim of the present study is a comprehensive analysis of DNA methylation alterations during HSC activation at a global and gene-specific level to elucidate their impact on hepatic stellate cell activation and to identify basic mechanisms of epigenetic control in adult stem cells during differentiation. (biomedcentral.com)
The results showed that YQRG effectively alleviated CCl 4 -induced liver injury and fibrosis in rats, including observations of improved liver function, decreased activity of hepatic stellate cells (HSCs), and decreased extracellular matrix (ECM) deposition. (biomedcentral.com)
The neural plexuses in the liver closely interact with liver sinusoidal cells, hepatic stellate cells (HSCs), Kupffer cells (KCs), and hepatic progenitor cells (HPC). (e-cmh.org)

There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by producing harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. (wanfangdata.com.cn)
Current 2D in vitro assays based on cell lines such as HepG2 that have reduced metabolic capacities compared to primary hepatocytes ex vivo, and the use of primary human hepatocytes suffers from high donor-to-donor variation and only retain in vivo characteristics for a short time ex vivo. (edu.au)
Therefore, for advancing further concepts in cell engraftment we studied vascular and related events in the liver after transplanting syngeneic hepatocytes into dipeptidyl peptidase IV-deficient rats. (elsevierpure.com)
However, incubation of hepatocytes with bosentan protected cells from cytokine toxicity in vitro and produced superior cell engraftment and proliferation in vivo. (elsevierpure.com)
In contrast, other liver cell types like hepatocytes and Kupffer cells did not show any significant changes in DNA methylation during culture. (biomedcentral.com)

Both cold and warm IRI activate the innate immune system, including liver Kupffer cells and neutrophils. (jci.org)
Activation of Kupffer cells and neutrophils leads to release of inflammatory cytokines and free radicals, which further aggravate liver injury [ 4 , 5 ]. (ijbs.com)

Cytokines involved in type 2 inflammation, such as IL-4, may also stimulate Kupffer cell proliferation. (wikipedia.org)
Zymosan A also raises cyclin D2 levels suggesting a role for the latter in macrophage activation besides proliferation. (wikipedia.org)
Inhibitory effect of sodium houttuyfonate on synovial proliferation in vitro in cells from a patient with rheumatoid arthritis. (spandidos-publications.com)
Injury to these cells result in the release of reactive oxygen species, proinflammatory signals, proliferation-associated cytokines, and the activation of repair pathways. (edu.au)
We treated rats with vascular drugs to define whether deleterious cell transplantation-induced events could be controlled followed by improvements in transplanted cell engraftment and proliferation. (elsevierpure.com)
CSF-1 signaling through CSF-1R regulates the proliferation and differentiation of cells in the monocytic lineage. (thermofisher.com)
In order to analyze the mechanism of DNA demethylation during HSC activation, the cell proliferation was examined by DNA synthesis determination via BrdU (5-bromo-2'-deoxyuridine) assay and Ki67 Western blot analysis. (biomedcentral.com)
However, β-AR agonist isoproterenol-mediated β-AR activation rescues acetaminophen (APAP)-induced liver injury by promoting HPC proliferation through Wnt signaling activation. (e-cmh.org)
Activation of M3 AChR plays an important role in cholangiocyte and HPC proliferation, anti-apoptosis, and liver regeneration [ 1 ]. (e-cmh.org)
Furthermore, IL-6 promotes hepatic FoxM1 activation that stimulates hepatocyte proliferation through signal transducers and activators of transcription 3 [ 8 ]. (e-cmh.org)

Involved inflammatory cells produce cytokines and chemokines, and generate ROS, further contributing to graft dysfunction. (jci.org)
Pleiotropic effects of IL-18 has also been reported, such as, enhancement production of IFN-gamma and GM-CSF in peripheral blood mononuclear cells, production of Th1 cytokines, IL-2, GM-CSF and IFN-gamma in T cells, enhancement of Fas ligand expression by Th1 cells. (rndsystems.com)
Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-α and activation of NF-κB after chronic ethanol feeding followed by in vitro stimulation with lipopolysaccharide (LPS). (uni-frankfurt.de)
Pancreatic acinar cell injury triggers the synthesis and release of pro-inflammatory cytokines and chemokines (32, 36, 39, 41, 82). (pancreapedia.org)
Another mechanism whereby injured pancreatic acinar cells trigger the inflammatory response is through synthesis and release of cytokines (36) and chemokines (11), and upregulation of adhesion molecules such as the intercellular adhesion molecule-1 (ICAM-1) (136), which together promote neutrophil and monocyte infiltration (27, 71) and exacerbate tissue injury (10, 27, 37). (pancreapedia.org)

Kupffer cells can be found attached to sinusoidal endothelial cells in both the centrilobular and periportal regions of the hepatic lobules. (wikipedia.org)

The authors found that liver grafts with absent carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) exhibited increased ischemia-reperfusion injury inflammation and decreased function in wild-type recipients. (jci.org)
In particular, we focus on the hypothesis that the macrophage is an important cell type in the propagation of inflammation and induction of insulin resistance in obesity. (jci.org)
We found cell transplantation altered liver gene expression related to vessel tone, inflammation, cell adhesion, thrombosis, or tissue damage/remodeling. (elsevierpure.com)
These drugs lowered hepatic ischemia and inflammation, whereas pretreatment of rats with the dual endothelin-1 receptor blocker, bosentan, improved cell engraftment independently of hepatic ischemia or inflammation, without improving liver repopulation. (elsevierpure.com)
Complement activation results in an enzymatic cascade leading to the production of opsonins and anaphylatoxins responsible for clearing pathogens and initiating inflammation. (ashpublications.org)

Hydrogen peroxide was used to induce an oxidative stress model of hepatocyte IAR-20 cells to evaluate the protective effects of BMMSCs in vitro. (medscimonit.com)

Despite high monocyte influx and maturation rates, hepatic Kupffer cell populations are tightly maintained. (wikipedia.org)

However, the ultimate fate of Kupffer cells in vivo is not yet fully understood. (wikipedia.org)
In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding on in vivo activation of NF-κB in NF-κB(EGFP) reporter gene mice. (uni-frankfurt.de)
An organoid cell culture is defined as a collection of cells culturing several cell types that develop from stem cells or organ progenitors and self-organise through cell sorting and spatially restricted lineage commitment, similar to organogenesis in vivo. (edu.au)
Liver organoids have demonstrated many advantages over conventional in vitro models such as long-term genetic stability, 2D in vivo-like organisation, and maintaining the necessary cellular cross talk and behavioural characteristics of their primary corresponding cells. (edu.au)
In response to cerulein (a CCK-8 ortholog widely used to elicit early pancreatitis responses in isolated acini an ex-vivo pancreatitis model), murine pancreatic acinar cells upregulate mRNA expression of both CXCL1 and CXCL2 within 90 min, with a supramaximally stimulating cerulein concentration of 0.1 mM producing 8 fold increase in CXCL1 and 10 fold increase in CXCL2 expression (87). (pancreapedia.org)
The production of lysozyme, previously considered a constitutive function of M phi, is therefore an indicator of M phi activation in vivo, where immunologically specific and nonspecific stimuli both stimulate lysozyme production at high levels in subpopulations of cells occupying discrete anatomical locations. (ox.ac.uk)

iii) Neonates and infants have higher stem/progenitor cell ratios, and thus transduction into stem/progenitor cells may occur more efficiently than in adults. (hindawi.com)

Kupffer cells are integral in the innate responses of the immune system. (wikipedia.org)
On the other hand, Ad vectors also have a number of disadvantages, including their low transduction efficiency in cells lacking coxsackievirus-adenovirus receptor (CAR) and their induction of innate immune responses. (hindawi.com)

Trim8 expression is mostly ubiquitous in murine and human tissues, and in epithelial and lymphoid cells, which can be induced by IFN-γ. (ijbs.com)

There they complete their differentiation into Kupffer cells. (wikipedia.org)
This activation of HSC is necessary to enable hepatic differentiation and is accompanied by changes in the expression of many genes such as extracellular matrix protein encoding genes [ 2 ]. (biomedcentral.com)

Initially quiescent HSC were activated in vitro by culturing the cells on a plastic surface in culture medium containing 10% fetal calf serum. (biomedcentral.com)
The analysis of global DNA methylation during in vitro activation of HSC by 5meC ELISA revealed a strong decrease of DNA methylation within three days of culture. (biomedcentral.com)
TAK1 was required for Trim8 function in hepatic I/R injury as TAK1 activation abolished Trim8 function in vitro . (ijbs.com)

Within 24 h of infection, cells found in the marginal zone of the spleen begin to produce lysozyme mRNA. (ox.ac.uk)
Later in the infection, other cells in the red and white pulp of the spleen, and cells in granulomas in the liver, become lysozyme-positive. (ox.ac.uk)

However, if resident Kupffer cell populations are depleted, monocytes derived from hematopoietic stem cells in the bone marrow and transported through blood circulation to the liver can also fully differentiate into true Kupffer cells. (wikipedia.org)
To improve the quality of liver grafts from extended-criteria donors donated after circulatory death (DCD), this study explored whether bone marrow mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP) have protective effects on DCD donor livers and the effects of ferroptosis in this procedure. (medscimonit.com)

Whether all these variable functions in the liver are mediated by different Kupffer cell subpopulations remains to be evaluated. (wanfangdata.com.cn)

Gut bacteria, bacterial endotoxins, and microbial debris transported to the liver from the gastrointestinal tract via the portal vein will first come in contact with Kupffer cells, the first immune cells in the liver. (wikipedia.org)
Because of this detection system, Kupffer cells play a critical role in initiating and mediating immune responses to bacterial infection of the liver. (wikipedia.org)
The adaptive immune system is also triggered, eliciting complement activation and T cell activation. (jci.org)
Chronic Granulomatous Disease , autoimmune diseases Autoimmune diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. (lecturio.com)
In the case of the CP, activation is driven by immune complexes containing complement-fixing antibodies. (ashpublications.org)

Short and long term effects of cytoskeleton-disrupting drugs on cytochrome P450 Cyp1a-1 induction in murine hepatoma 1c1c7 cells: suppression by the microtubule inhibitor nocodazole. (aspetjournals.org)
Lysozyme is an inducible marker of macrophage activation in murine tissues as demonstrated by in situ hybridization. (ox.ac.uk)

this tissue represents scarring in response to chronic, repeated liver cell injury. (msdmanuals.com)
2. Tissue injury and inflammatory cell recruitment. (pancreapedia.org)
Hepatic fibrosis is an abnormal wound-healing process in which hepatic parenchymal cells (HPCs) transform into fibrous tissue of ECM [ 1 , 2 , 3 ], which is detrimental to human health. (biomedcentral.com)

Periportal Kupffer cells tend to be larger and have more lysosomal enzyme and phagocytic activity, whereas centrilobular Kupffer cells create more superoxide radical. (wikipedia.org)

After cell transplantation in hepatic sinusoids, perturbations in hepatic microcirculation along with changes in various liver cell types are among the earliest changes. (elsevierpure.com)

HUANG Zhenkai,DING Wei.Study on the Mechanism of Curcumin Inhibiting the Activation of Kupffer Cells[J].Western Journal of Traditional Chinese Medicine,2021,34(08):16-20. (paperopen.com)
Iron-containing particles have been proposed as a mechanism of introducing unregulated iron into cells, and soluble iron has been shown to induce the expression ofTNF-a in Kupffer cells, which was preceded by an increase in hydroxyl radicals. (cdc.gov)

Importantly, Kupffer cells express the SR-AI/II scavenger receptor. (wikipedia.org)
2003). "Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion are down-regulated by lung collectin surfactant protein A". J. Immunol. (wikipedia.org)
The D2S and D2L dopamine receptor isoforms are differentially regulated in Chinese hamster ovary cells. (aspetjournals.org)
Treatment of rats before cell transplantation with the angiotensin converting enzyme blocker, lisinopril, or angiotensin II receptor blocker, losartan, did not improve cell engraftment. (elsevierpure.com)

In ITP, for example, his laboratory is interested in how platelet antigens are processed and presented by antigen-presenting cells to activate T lymphocytes. (lu.se)

Thus, the regulatory role of these cell types in the liver is important for metabolic clearance of exogenous toxins. (biomedcentral.com)
Cross-resistance to antitumor diarylsulfonylureas and collateral sensitivity to mitochondrial toxins in a human cell line selected for resistance to the antitumor agent N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)urea. (aspetjournals.org)

Reactions were assessed by measuring TNFα and TGFβ in supernatants of cells for which mRNA expressions for Srebp-1c and PPARα were determined in parallel. (frontiersin.org)
Lysozyme mRNA levels in liver granulomas remain relatively constant during the infection, and lysozyme is produced by most granuloma cells. (ox.ac.uk)
This contrasts with tumor necrosis factor alpha (TNF alpha) mRNA, which is produced by fewer cells in the granuloma, and which can be massively induced by lipopolysaccharide administration. (ox.ac.uk)

HCV can also be detected in the peripheral blood, particularly in mononuclear cells. (medscape.com)

Epinephrine (EPI) and norepinephrine (NE) induce the production of collagen-1α2 (COL1A2), transforming growth factor-beta (TGF-β), and induce the activation of NF-κB by acting on HSCs [ 1 , 3 ]. (e-cmh.org)

The function of global DNA demethylation in adult stem cells are currently unknown, but global DNA demethylation events are under investigation during zygote formation and primordial germ cell migration in early embryogenesis, where they are linked to cellular reprogramming and pluripotency [ 4 ]. (biomedcentral.com)

It is because of this that any change to Kupffer cell functions can be connected to various liver diseases such as alcoholic liver disease, viral hepatitis, intrahepatic cholestasis, steatohepatitis, activation or rejection of the liver during liver transplantation and liver fibrosis. (wikipedia.org)
However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. (wanfangdata.com.cn)

Fibrotic livers are characterized by an inflammatory microenvironment that is composed of various immunologically active cells, including liver-resident populations (e.g. (mdpi.com)

By contrast, direct-acting nitroglycerine or prostacyclin improved cell engraftment and also kinetics of liver repopulation. (elsevierpure.com)

Activation of the TFEB-lysosome pathway is important in regulating autophagy and apoptosis. (biomedcentral.com)

They are also useful in removing apoptotic cells from circulation. (wikipedia.org)

The essential components include inflammatory cell infiltrate and hepatocellular injury with predominantly lobular involvement. (medscape.com)
Moreover, the SNS promotes liver inflammatory microenvironment formation and hepatocellular carcinoma development by regulation of interleukin (IL)-6 and TGF-β through activation of α1-AR on KCs [ 4 ]. (e-cmh.org)

Conclusion Curcumin could reduce the secretion of proinflammatory factors and chemokines which might be through inhibiting the activation of KCs, therefore to relieve acute liver injury. (paperopen.com)

Old or defective cells are removed through apoptosis, as well as through being phagocytized by neighbouring Kupffer cells. (wikipedia.org)

Zymosan is prepared from yeast cell wall and consists of protein-carbohydrate complexes. (wikipedia.org)

1-3 In such indications, therapeutic intervention by preventing complement activation may have clinical utility. (ashpublications.org)

Furthermore, we show that by preventing CP activation, TNT003 also prevents cold agglutinin-driven generation of anaphylatoxins. (ashpublications.org)

BMMSCs showed significant protective effects on the ultrastructure of DCD donor livers and ROS-induced injury to IAR-20 cells under electron microscopy. (medscimonit.com)
In conclusion, our study demonstrates that Trim8 deficiency plays a protective role in hepatic I/R injury by inhibiting the activation of TAK1-dependent signalling pathways. (ijbs.com)
Hepatic I/R injury is characterized by endothelial and Kupffer cell swelling, vasoconstriction, leukocyte infiltration, and platelet aggregation in sinusoids [ 3 ]. (ijbs.com)

These cells produce excessive amounts of abnormal matrix (consisting of collagen, other glycoproteins, and glycans) and matricellular proteins. (msdmanuals.com)

Methods Primary KCs cells were isolated from mice liver by in situ perfusion and gradient centrifugation, pretreated with different concentrations of curcumin and cultured for 24 hours after adding LPS. (paperopen.com)

however, animal and cell models remain critical in furthering our understanding of molecular mechanisms, signaling pathways, and new drug targets. (pancreapedia.org)
Mechanistically, our study suggests that Trim8 deficiency may elicit hepatic protective effects by inhibiting the activation of transforming growth factor β-activated kinase 1 (TAK1)-p38/JNK signalling pathways. (ijbs.com)
Activation of the different pathways is mediated by pathway-specific proteins that recognize molecular patterns on pathogens. (ashpublications.org)

Moreover, parasympathetic nerve-secreted acetylcholine (Ach) inhibits expression of tumor necrosis factor (TNF) and IL-6 through activation of Src kinase by acting on the α7AChR of KCs, thus suppressing lipopolysaccharide-induced hepatitis [ 7 ]. (e-cmh.org)

The primary function of the Kupffer cell is to remove foreign debris and particles that have come from the hepatic portal system when passing through the liver. (wikipedia.org)

The study found that both liver cell models showed ATP metabolism disorder, membrane damage, autophagosome formation and lysosome damage, but the difference was that, KUP5 cells exhibited more serious damage than AML12 cells, suggesting that immunogenic cell type is particularly sensitive to CDs. (biomedcentral.com)
The advantages of 3D models include replicating the complex attributes of the liver beyond liver specific metabolism, such as increased cell density, organisation, and cell-cell signalling, O2 zonation, as well as the anatomy of the liver lobule and the circulatory system. (edu.au)

These and adjacent cells proliferate, becoming contractile cells termed myofibroblasts. (msdmanuals.com)

Macrophages20

Stellate13

Hepatocytes5

Neutrophils2

Proliferation10

Cytokines5

Endothelial cells1

Inflammation5

Oxidative Stress1

Maturation1

Vivo6

Progenitor cells1

Innate2

Epithelial1

Differentiation2

Vitro3

Spleen2

Bone marrow2

Subpopulations1

Immune5

Murine2

Tissue3

Phagocytic1

Liver cell types1

Mechanism2

Receptor4

Antigen prese1

Toxins2

MRNA3

Mononuclear cells1

Induce1

Cellular1

Fibrosis2

Immunologically1

Contrast1

Regulating autophagy1

Apoptotic1

Hepatocellular2

Chemokines1

Apoptosis1

Complexes1

Complement activation1

Prevents1

Injury3

Collagen1

Perfusion1

Pathways3

Tumor1

Debris1

Metabolism2

Myofibroblasts1