Hepatitis Kupffer cell

R. B. Sewell, N. D. Yeomans, D. J. Morgan, and R. A. Smallwood, Hepatic Kupffer cell function the efficiency of uptake and intracellular degradation of C labeled mitochondria is reduced in aged rats. Mech Ageing Dev 73(3) 157-168 (1994). 

Gut-associated lymphoid tissue (GALT) Secretory immunoglobulin A Hepatic Kupffer cells... 

Rusyn, L, Bradham, C. A., Cohn, L., Schoonhoven, R., Swenberg, J. A., Brenner, D. A., and Thurman, R. G. (1999). Corn oil rapidly activates nuclear factor-kappaB in hepatic Kupffer cells by oxidant-dependent mechanisms. Carcinogenesis 20, 2095-2100. 

The uptake of poly-2-vinylpyridine-l-oxide into ly-sosomes of alveolar macrophages of rats (Grund-MANN 1967) mi guinea pigs (Beck and Boje 1967) and hepatic Kupffer cells of mice (Bairati and Castano 1968) has been documented. 

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. 

Blood flowing from the intestines to the liver through the hepatic portal vein often contains bacteria. Filtration of this blood is a protective function provided by the liver. Large phagocytic macrophages, referred to as Kupffer cells, line the hepatic venous sinuses. As the blood flows through these sinuses, bacteria are rapidly taken up and digested by the Kupffer cells. This system is very efficient and removes more than 99% of the bacteria from the hepatic portal blood. 

Figure 8.1 Body iron stores and daily iron exchange. The figure shows a schematic representation of the routes of iron movement in normal adult male subjects. The plasma iron pool is about 4 mg (transferrin-bound iron and non-transferrin-bound iron), although the daily turnover is over 30 mg. The iron in parenchymal tissues is largely haem (in muscle) and ferritin/haemosiderin (in hepatic parenchymal cells). Dotted arrows represent iron loss through loss of epithelial cells in the gut or through blood loss. Numbers are in mg/day. Transferrin-Tf haemosiderin - hs MPS - mononuclear phagocytic system, including macrophages in spleen and Kupffer cells in liver.

Callery, M., Mangino, M., and Flye, M., Kupffer cell prostaglandin-E2 production is amplified during hepatic regeneration, Hepatology, 14, 368, 1991. 

A wide spectrum of hepatic lesions has been reported in AIDS (H4), but it is not known whether the changes are related to the presence of HIV-1. Therefore, sections from livers of autopsied patients with AIDS were examined for the presence of HIV-1 antigen p 24 (core) and gp 41 (envelope) by the avidin-biotin-peroxidase complex methods using monoclonal antibodies. The most common histologic abnormalities were steatosis, portal inflammation, Kupffer cell hyperplasia, and focal hepatocellular and bile duct damage. Immunoreactivity for HIV-1 antigens was demonstrated in 80% of cases. 

Hepatic Effects. Hepatic effects have been reported in humans exposed orally or by the dermal and inhalation routes to toxic doses of 1,2-dibromoethane (Letz et al. 1984 Olmstead 1960 Saraswat et al. 1986). These effects consist of hepatocellular and Kupffer cell necrosis. Results in humans are supported by animal studies in which the liver is also a target organ for toxic effects of 1,2-dibromoethane following exposure by a variety of routes (Botti et al. 1986 Brandt et al. 1987 Broda 1976 NTP 1982 Rowe et al. 1952). 1,2-Dibromoethane, as well as inducing necrosis, can also act as a hepatocellular mitogen in rats (Ledda-Columbano et al. 1987a). 

Cell Specific Delivery of Anti-Inflammatory Drugs to Hepatic Endothelial and Kupffer Cells for the Treatment of Inflammatory Liver Diseases... 

Figure 4.1. Schematic representation of the architecture of the liver. Blood enters the liver through the portal vein (PV) and hepatic arteries (HA), flows through the sinusoids, and leaves the liver again via the central vein (CV). KC, Kupffer cells SEC, sinusoidal endothelial cells HSC, hepatic stellate cells BD, bile duct. Modified from reference 98.

Figure 4.2. Diagram outlining the pathogenesis of liver fibrosis. Injury to parenchymal cells (PC) results in the activation of Kupffer cells (KC) and sinusoidal endothelial cells (SEC) and the recruitment of inflammatory cells (IC). These cells release cytokines, growth factors and reactive oxygen species that induce activation and proliferation of hepatic stellate cells (HSC). HSCs gradually transform into myofibroblasts (MF), the major producers of extracellular matrix (ECM) proteins.

The use of the reticulo-endothelial system (RES) was the first approach to liver contrast agents. As an adjunct, spleen imaging would also be possible with a contrast agent that is taken up by the RES. The Kupffer cells of the liver, which represent 10% of all hepatic cells, constitute the major portion (80-90%) of all fixed macrophages and they are extremely effective in the phagocytosis of all types of particles. The downside of the use of this mechanism, however, is the concomitant release of toxic mediators that might and - as a matter of fact - often has made this approach non-feasible. Adverse events provoked by the mediators are changes in blood pressure (most often hypotension) and fever. 

As an example, acetaminophen (APAP) in overdose has been used by several groups to identify hepatotoxicity biomarkers in mice. APAP-induced hepatotoxicity is characterized by hepatic centrilobular necrosis and hepatitis. APAP biotransformation by Phase I enzymes leads to the formation of the reactive metabolite N-acetyl-p-benzoquinone (NAPQI), which can deplete glutathione and form adducts with hepatic proteins (see Section 15.2). Protein adduction primes the hepatocytes for cytokines released by activated macrophages (Kupffer cells) and/or destructive insults by reactive nitrogen species. Although necrosis is recognized as the mode of cell death in APAP overdose, the precise mechanisms are still being elucidated [152]. 

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