Kupffer

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Federal government websites often end in. The site is secure. Kupffer cells are resident liver macrophages and play a critical role in maintaining liver functions. Under physiological conditions, they are the first innate immune cells and protect the liver from bacterial infections. Under pathological conditions, they are activated by different components and can differentiate into M1-like classical or M2-like alternative macrophages. The metabolism of classical or alternative activated Kupffer cells will determine their functions in liver damage. Special functions and metabolism of Kupffer cells suggest that they are an attractive target for therapy of liver inflammation and related diseases, including cancer and infectious diseases.

Kupffer

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. Kupffer cells comprise the largest population of tissue-resident macrophages in the body. 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. 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. Kupffer cells can be found attached to sinusoidal endothelial cells in both the centrilobular and periportal regions of the hepatic lobules. Kupffer cell function and structures are specialized depending on their location. Periportal Kupffer cells tend to be larger and have more lysosomal enzyme and phagocytic activity, whereas centrilobular Kupffer cells create more superoxide radical. Kupffer cells are amoeboid in character, with surface features including microvilli , pseudopodia and lamellipodia , which project in every direction. The microvilli and pseudopodia play a role in the endocytosis of particles. Notable cytoplasmic elements include ribosomes , Golgi complexes , centrioles , microtubules and microfilaments. Kupffer cells also contain rough endoplasmic reticulum , a nuclear envelope , and annulate lamellae , all of which demonstrate peroxidase activity. This receptor is involved in recognising and binding the lipid A domain of lipopolysaccharide LPS and lipoteichoic acid. Lipopolysaccharide LPS is a bacterial endotoxin which is found in the cell wall gram-negative bacteria , whereas lipoteichoic acid is present in gram-positive bacteria. Because of this detection system, Kupffer cells play a critical role in initiating and mediating immune responses to bacterial infection of the liver.

Perhaps these apparently conflicting kupffer sets can be largely reconciled by a threshold hypothesis; excessive or prolonged release of Kupffer cell mediators can switch a protective mechanism to a damaging inflammatory response, kupffer.

Sponsored by the Carcinogenesis Speciality Section. Ruth A. Roberts, Patricia E. Ganey, Cynthia Ju, Lisa M. Kamendulis, Ivan Rusyn, James E. Kupffer cells are resident macrophages of the liver and play an important role in its normal physiology and homeostasis as well as participating in the acute and chronic responses of the liver to toxic compounds. Activation of Kupffer cells directly or indirectly by toxic agents results in the release of an array of inflammatory mediators, growth factors, and reactive oxygen species.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Kupffer cells are a specialized population of macrophages that reside in the liver. They remove microbial products and other noxious substances that are delivered to the liver via the blood. A landmark study reveals how Kupffer cells, resident macrophages of the liver, can promote antitumor immunity. Central to this function is ID3, a Kupffer cell lineage-determining factor. The findings provide new insights into cancer therapy. Whether Kupffer cells play a role in regulating the pathogenesis of fatty liver disease remains to be completely explored.

Kupffer

Federal government websites often end in. The site is secure. Kupffer cells are a critical component of the mononuclear phagocytic system and are central to both the hepatic and systemic response to pathogens. Kupffer cells are reemerging as critical mediators of both liver injury and repair.

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Another indirect mechanism of KC action against tumor cells is the secretion of IL, which recruits and induces NK cell cytotoxicity [ ]. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Macrophage plasticity and polarization: in vivo veritas. Four different stages of liver metastasis have been identified: 1 the microvascular phase, which implicates tumor cell arrest in the sinusoidal vessels, tumor cell death or extravasation; 2 the extravascular, preangiogenic phase, during which host stromal cells are recruited into avascular micrometastases; 3 the angiogenic phase, the stage which recruits endothelial cells and tumors become vascularized; and 4 the growth phase, which leads to establishment of clinical metastases [ ]. Chem Res Toxicol. For example, macrophages associated with the spontaneous resolution of hepatic fibrosis and have been termed scar-associated macrophages SAMs by the Iredale group Kupffer cell oxidant production is central to the mechanism of peroxisome proliferators. Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity. The reader may like to weigh these two hypotheses as the specific examples are presented. Nucleotide-binding oligomerization domain-2 modulates specific TLR pathways for the induction of cytokine release. Hepatocyte injury by activated neutrophils in vitro is mediated by proteases. Genotoxic agents induce tumors by increasing rates of DNA damage, whereas nongenotoxic carcinogens act to promote the spontaneous or accumulated DNA damage present in all tissues. Nagy LE. S2CID Further studies on this potentially important interaction are clearly required at this point.

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PMC Copyright notice. This symposium provided an exciting opportunity to review the state of our knowledge and also facilitated such cross-fertilization giving new ideas and strategic direction. On the other hand, depletion of Kupffer cells increases liver injury from partial hepatectomy Prins et al. PMID These data suggest that alternative M2 macrophages played a pro-fibrogenesis role and were resorbed as soon as the liver fibrosis resolution started. The role of Kupffer cell oxidant production in early ethanol-induced liver disease. Recognizing the potential limitations of these approaches, we have adopted a protocol that utilizes clodronate-encapsulated liposomes to deplete Kupffer cells in vivo vanRoojen et al. Role of Kupffer cells in the pathogenesis of liver disease. Fibrosis will eventually cause cirrhosis , a loss of function of the liver due to extensive scarring. Kupffer cells, as the largest population of tissue resident macrophages, not only play an important role in first-line defense against invading pathogens, but may also act as APCs to activate and regulate T-cell responses. These findings suggest that Kupffer cells have some ability to act as APCs but are only partially competent due to their insufficient expression of costimulatory molecules. Tolerance Induction in Liver. You have entered an invalid code. Nat Med. Interleukin signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice.