Kupfer cells

Small molecules are eliminated from the body largely by means of drug metabolism enzymes in the liver and other tissues and by urinary excretion. Large molecules are also eliminated by renal and hepatic mechanisms. Proteins that are less than 40 to 50 kDa are cleared by renal filtration with little or no tubular reabsorption. Larger proteins are less likely to be filtered but may be subject to phagocytosis in hepa-tocytes and Kupfer cells in the liver. Protein biotransformation—denaturation, proteolysis, and oxidative metabolism—is also important. 

Mild liver dysfunction, hypophosphatemia, and hypomag-nesmia are the most common laboratory abnormahties caused by aldesleukin (76,77). About 20% of patients develop mild to severe intrahepatic cholestasis with reversible and dose-dependent rises in bilirubin and alkahne phosphatase while serum transaminases were only shghtly increased (4,78). Recurrence of cholestasis after aldesleukin rechallenge was not always observed (79). The mechanism of aldesleukin-induced intrahepatic cholestasis is unknown, but it might be mediated by activation of Kupfer cells and the subsequent release of cytokines (SEDA-20, 335). Focal fatty infiltrates of the liver mimicking metastases were also reported in a patient receiving both aldesleukin and a short course of interferon alfa (80). 

It has been observed that the content of liver ferritin in adult female rats is more than twice that in male rats (31). The level of ferritin in both sexes is low until about 7 weeks after birth from then on the levels in both increase, but the level in females rises about twice as rapidly as that in males (32). An analysis of the distribution of ferritin in liver cells has shown that it is almost exclusively confined to hepatocytes whereas the Kupfer cells seem to be the major site of haemosiderin deposition (33). 

Rahman YE, Cerney EA, Patel KR, et al. Differential uptake of liposomes varying in size and lipid composition by parenchymal and Kupfer cells of mouse liver. Life Sci 1982 31 2061-2071. 

Kunitz-type inhibitor 1027 Kupfer cells 1511 KvLQTl 59 Kybemin 458, 1004 Kybemin P 1008 KyberSept trial 997... 

Hepatic metabolism is important to the clearance of therapeutic proteins with molecular weights greater than 20kD, although renal clearance can contribute to proteins as large as 50 kD. The Kupfer cell and hepatocytes of the liver are involved in clearing protein drugs. 

Wu J, Li J, Salcedo R, Mivechi NF, Trinchieri G, Horuzsko A. The Hoinffammatory myeloid cell receptor TREM-1 controls Kupfer cell activation and development of hepatocellular carcinoma. Cancer Res. 2012 72 3977-86. 

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