Receptor scavenger

CD163 (Scavenger receptor) Adhesion molecules (ICAM-1, E-selectin)... 

Jessup W, Gelissen IC, Gaus K, Kritharides L (2006) Roles of ATP binding cassette transporters Al and Gl, scavenger receptor BI and membrane lipid domains in cholesterol export from macrophages. Curr Opin Lipidol 17(3) 247-57... 

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

In tissues, cholesterol balance is regulated as follows (Figure 26-5) Cell cholesterol increase is due to uptake of cholesterol-containing Hpoproteins by receptors, eg, the LDL receptor or the scavenger receptor uptake of free cholesterol from cholesterol-rich hpoproteins to the cell... 

Fig. 2.1 Sequence of events in atherogenesis and role of low-density lipoprotein. Native LDL, in the subendothelial space, undergoes progressive oxidation (mmLDL) and activates the expression of MCP-1 and M-CSF in the endothelium (EC). MCP-1 and M-CSF promote the entry and maturation of monocytes to macrophages, which further oxidise LDL (oxLDL). Ox-LDL is specifically recognised by the scavenger receptor of macrophages and, once internalised, formation of foam cells occurs. Both mmLDL and oxLDL induce endothelial dysfunction, associated with changes of the adhesiveness to leukoc)des or platelets and to wall permeability.

FIGURE 3.2.2 Metabolic pathways of carotenoids such as p-carotene. CM = chylomicrons. VLDL = very low-density lipoproteins. LDL = low-density lipoproteins. HDL = high-density lipoproteins. BCO = p-carotene 15,15 -oxygenase. BCO2 = p-carotene 9, 10 -oxygenase. LPL = lipoprotein lipase. RBP = retinol binding protein. SR-BI = scavenger receptor class B, type I. 

Kiefer, C. et al., A class B scavenger receptor mediates the cellular uptake of carotenoids iu Drosophila, Proc. Natl. Acad. ScL USA, 16, 10581, 2002. 

Van Bennekum, A. et al.. Class B scavenger receptor-mediated intestinal absorption of dietary P-carotene and cholesterol, Biochem., 44, 4517, 2005. 

Reboul, E. et al.. Lutein transport by Caco-2 TC-7 cells occurs partly by a facilitated process involving the scavenger receptor class B type 1 (SR-Bl), Biochem. J., 387, 455, 2005. 

Altmann, S.W. et al.. The identification of intestinal scavenger receptor class B, type 1 (SR-Bl) by expression cloning and its role in cholesterol absorption, Biochim. Biophys. Acta, 1580, 77, 2002. 

The reactions described so far do not require the involvement of the apo-B protein, neither would they necessarily result in a significant amount of protein modification. However, the peroxyl radical can attack the fatty acid to which it is attached to cause scission of the chain with the concomitant formation of aldehydes such as malondialdehyde and 4-hydroxynonenal (Esterbauer et al., 1991). Indeed, complex mixtures of aldehydes have been detected during the oxidation of LDL and it is clear that they are capable of reacting with lysine residues on the surface of the apo-B molecule to convert the molecule to a ligand for the scavenger receptor (Haberland etal., 1984 Steinbrecher et al., 1989). In addition, the lipid-derived radical may react directly with the protein to cause fragmentation and modification of amino acids. 

Graham, A., Hogg, N., Kalyanaraman, B., O Leary, V.J., Darley-Usmar, V. and Moncada, S. (1993). Peroxynitrite modification of low density lipoprotein leads to recognition by the macrophage scavenger receptor. FEBS Lett. 330, 181-185. 

Haberland, M.E., Olch, C.L. and Fogelman, A.M. (1984). Role of lysines in mediating interaction of modifed low density lipoproteins with the scavenger receptor of human monocyte macrophages. J. Biol. Chem. 259, 11305-11311. 

Parthasarathy, S., Printz, D.J., Boyd, D., Joy, L. and Steinberg, D. (1986). Macrophage oxidation of LDL generates a modified form recognised by the scavenger receptor. Arteriosclerosis 6, 505-510. 

Steinbrecher, U.P., Lougheed, M., Kwan, W.-C. and Dirks, M. (1989). Recognition of oxidised low density lipoprotein by the scavenger receptor of macrophages results from the derivatisa-tion of apo lipoprotein B. J. Biol. Chem. 264, 15216-15233. 

LDL extracted from human or animal atherosclerotic lesions has been shown to be taken up much fester than plasma LDL by macrophages by means of their scavenger receptors. 

It is unlikely that the damaging effects of ox-LDL are relevant only to the walls of blood vessels and there is no reason to suppose they are confined to one disease. The initial histopathologjcal sign of coronary heart disease is the appearance of the fetty streak on the luminal surfece of arteries. Fatty streaks are composed of aggregated macrophages that have taken up ox-LDL via the scavenger receptor. Recently, we have detected such foam cells in the rheumatoid synovium (Section 5.5). 

The LDL particle, which has been oxidatively modified by the mechanisms described above, is no longer recognized by the classic LDL receptor and is taken up by the macrophage scavenger receptor. Importantly, ox-LDL also exhibits a variety of pro-inflammatory activities, as described below. 

Geng YJ, Holm J, Nygren S, Bruzelius M, Stemme S, Hansson GK. Expression of the macrophage scavenger receptor in atheroma—relationship to immune activation and the T-cell cytokine interferon-gamma. Arterioscler Thromb Vase Biol 1995 15(11) 1995-2002. 

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