Kupffer cell activity

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

If the ATP depletion is too great, then apoptosis cannot proceed. Kupffer cell activation involving IFNy (interferon) and TNF-a is part of an inflammatory response in which nitric oxide and various cytokines are produced. 

The reaction that produces NAPQI generates superoxide anions as a by-product. Interactions of NAPQI with other cellular molecules also generate reactive oxygen species, leading to oxidative stress on the hepatocyte (Zimmerman, 1999 Dahm and Jones, 1996). The role of calcium and Kupffer cell activation have been impUcated as contributing factors for acetaminophen-induced liver injury by producing reactive nitrogen species (Treinen-Moslen, 2001). 

These various imaging techniques (s. tab. 8.1) - as well as some nuclear medicine-based methods (see chapter 9) - enable key features of benign and malignant tumours to be recognized, including (7.) vascularity, (2.) internal structure, (2.) hepatocyte functions, (4.) biliary tract, (5.) bile secretion, (d.) calcification, and (7.) Kupffer cell activity. 

Fig. 22.13 Late stage of acute viral hepatitis B moderate roundcell infiltration of the lobular parenchyma with small aggregates of Kupffer cells and Kupffer cell activation slight disarray of liver cell trabeculae minimal canalicular cholestasis (— ) liver cell mitosis ( ) and binuclear hepatocytes...

Su GL (2002) Lipopolysaccharides in liver injury molecular mechanisms of Kupffer cell activation. Am J Physiol Gastrointest Liver Physiol 283 G256-G265... 

Many studies focused on growth factors derived from the Kupffer cell. Activated NPCs, particularly Kupffer cells, produce cytokines such as TNFa, interleukin-la, and interleukin-Ip (ILla, ILIP). These cytokines affect the fate of neighboring hepatocytes. TNFa is able to increase hepatocyte proliferation and suppress apoptosis in cultured rodent hepatocytes (Holden et al. 2000 Rolfe et al. 

NAPBQl is an electrophile and as such will cause oxidative damage to cellular nucleophiles. This in turn will initiate a cascade of free radicals to be formed with the consequential oxidative damage resulting from these events. In addition, inhibition of ATP synthetase will result in a decrease in cellular ATP concentrations, mitochondrial dysfimction and more free radical formation. Other workers have put forward alternative hypotheses to the above two, and these include disruption of calcium homeostasis, altered mitochondrial function, Kupffer cell activation, protein nitrosylation, activation of inflammatory mediators, damage to DNA and apoptosis to name but a few ... 

Kupffer cells Activates B cells, induces antibody class-switching... 

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