Kupffer cells binding

Suramin is not absorbed from the intestinal tract and is administered intravenously. Although the initial high plasma levels drop rapidly, suramin binds tightly to and is slowly released from plasma proteins, and so it persists in the host for up to 3 months. Suramin neither penetrates red blood cells nor enters the CNS. It is taken up by the reticuloendothelial cells and accumulates in the Kupffer cells of the liver and in the epithelial cells of the proximal convoluted tubules of the kidney. It is excreted by glomerular filtration, largely as the intact molecule. 

M. van Oosten, E. van de Bilt, T. J. C. Van Berkel, and J. Kuiper. New scavenger receptor-like receptors for the binding of lipopolysaccharide to liver endothelial and Kupffer cells, Infect. Immun. 66 5107-5112 (1998). 

H. Senoo, S. Smeland, E. Stang, N. Roos, T. Berg, K. R. Norum, and R. Blomhoff, Stellate cells take up retinol-binding protein, Cells of the Hepatic Sinusoid (D. L. Knook, E. Wisse, eds.), Kupffer Cell Foundation, Leiden, 1993, pp. 423-425. 

Mononuclear phagocytes (macrophages, Kupffer cells, spleen or lymph node) and sinusoidal or other specialized endothelium remove IgG from plasma, most frequently as IgG-containing immune complexes, IgG aggregates, or IgG bound to cell-associated epitopes [66-69], The initial binding event often occurs between the Fc portion of the IgG molecule and specific Fc receptors (FcyR) on reticuloendothelial cells (Figure 11.2). 

Fig. 9 Possible mechanisms for cell-mediated immune responses triggered by reactive metabolites. The covalent binding of the reactive metabolite modifies hepatic proteins. The death or alteration of one hepatocyte due to mild direct toxicity may lead to the extrusion of a modified protein through the fenestrae of sinusoidal endothelial cells (SEC). The uptake of this haptenized protein by an antigen-presenting cell (APC), such as a Kupffer cell, may lead to the presentation of a metabolite-bound peptide on a major histocompatibility (MHC) class II molecule of the APC, and the recognition of this modified peptide by the T cell receptor (TCR) of a helper T cell. The latter may then provide help to a cytotoxic T lymphocyte recognizing modified peptides presented on the MHC class I molecules of hepatocytes...

Treatment of animals with large doses of retinol stimulated Kupffer cell functions including phagocytic activity and release of tumour necrosis factor and superoxide anion (Oj ) (Mobley et al. 1991). Ohata et al. (2000) reported mRNA by rat Kupffer cells of retinoic acid receptor and retinoid X receptor subtypes and their binding activities to the retinoic acid responsive element or retinoid X responsive element. 

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