Distribution receptor-mediated endocytosis

In Chapter 14, it was explained that the lipid composition of LCM (cf. Section 12.1) is similar to the lipid composition of both chylomicron remnant particles (cf. Section 14.2.1) and LDL particles (cf. Section 14.1). Based upon this molecular similarity, it was proposed that i.v. injected LCM could readily bind (as do chylomicron remnants) to apolipoprotein E in the bloodstream (cf. Section 14.2.1). Both the LDL receptor (a.k.a. apo B,E receptor ) and the LRP (cf. Section 14.2.1) have a high affinity for apo E (ref. 666), and both receptors play an essential role in the receptor-mediated endocytosis of chylomicron remnants (ref. 650,665,709). Accordingly, these two endocytic pathways have been proposed (together with scavenger receptor-mediated endocytosis) to influence LCM distribution in vivo in certain pathological states (cf. above). 

Gene delivery systems can distribute plasmids to the desired target cells, after which the plasmid is internalized into the cell by a number of mechanisms, such as adsorptive endocytosis, receptor-mediated endocytosis, micropinocytosis, caveolae-mediated endocytosis and phagocytosis (see Section 1.3.3.2). The intracellular fate of plasmids depends on the means by which they are internalized and translocated to the cytoplasms and then to the nucleus. In coated-pit endocytosis, DNA complexes first bind to the cell surface, then migrate to clathrin-coated pits about 150 ran in diameter and are internalized from the plasma membrane to form coated vesicles. 

In hepatocytes, vitamin E can take two routes. A fraction of it is packaged as VLDL and reenters the circulation, while excess is excreted in the bile. Plasma lipolysis of the VLDL particle again results in release not only of lipids, but also of vitamin E, with the remainder left with the LDL particles. This fraction can be further distributed to tissues via LDL receptor-mediated endocytosis or transferred between lipoproteins, mainly to HDL, by plasma lipid transfer proteins. Thus, mobilization of vitamin E from intestinal and liver... 

Active transport and receptor-mediated uptake also may influence the biodistribution of macromolecules. For example, the internalization of monoclonal antibodies into cells may occur via Fey receptors, found on various immune and hematopoietic cells [9], or binding to membrane-localized antigens [10]. Thus, active uptake processes can serve to increase the volume of distribution to a large extent relative to that which would be expected based only on physico-chemical properties. Receptor-mediated endocytosis may represent a significant elimination pathway as well (see the Receptor-mediated elimination subsection) and is recognized as a major process influencing the overall disposition of macromolecules [11]. 

The observations described above have important implications with regard to actinide/lanthanide distributions within the body. It is apparent that in binding to transferrin, the f elements are participating in certain aspects of the iron transport pathways in vivo. However, no plutonium, e.g., is found within red blood cells following incorporation and there is no unequivocal evidence that plutonium and the other actinides or lanthanides are transported into cells via transferrin-receptor-mediated endocytosis (Duffield and Taylor 1986). This, too, is a puzzling aspect of f-element-transferrin chemistry and biochemistry which needs more study. 

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