Kuppfer cells

Particulates in the size range of 0.1-7 /an tend to be cleared by the MPS, localizing predominantly in the Kuppfer cells of the liver. 

Figure 22.2 Fates of nanoparticulates after i.v. injection and local administration to the target tissue. After i.v. injection, the particles should avoid aggregation and embolization to avoid entrapment into the lung capillaries. Kuppfer cells of the liver phagocytose major part of the nanoparticulate dose (illustrated on the right), but this may be slowed down by nanoparticulate surface modifications. Inthetargettissue (on the left), the nanosystem should enter the vascular endothelial cells, if they are the target cells, like in the case of neovascularization. Otherwise, they should escape from the vasculature, dock to the...

The DNA is rapidly eliminated from the compartment into which it is administered as a result of both degradation through endo- and exonucleases and distribution to other compartments. The DNA is eliminated from the blood compartment by interaction with Kuppfer cells through a specific scavenger/ receptor interaction (173). An intravenously administered asialo-orosomucoid-polylysine-DNA complex is cleared from the blood with an apparent half-life of 2.5 min (174). The DNA taken up by the liver is eliminated with a half life of 1.0 to 1.3 hours, gene transcripts were evident for 1 to 12 hours, and the gene product persisted for 6 to 24 hours. 

PPARs enhance cholesterol efflux and stimulate critical steps of the reverse cholesterol transport pathway (reviewed in ref. 507). PUFA and activating PPAR increase hepatic cholesterol uptake. PPARy induces expression of SR B1 in rat hepatocytes, liver EC, and Kuppfer cells (508). PPARa activation in human macrophages and foam cells results in an enhanced availability of free cholesterol for efflux through the ABCAl pathway by reducing cholesterol esterification rates and ACATl activity (509). 

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