Degradation of normal and abnormal plasma lipoproteins by cultured macrophages.
Degradation of plasma lipoproteins via LDL-receptor-mediated endocytosis is carefully regulated and does not lead to the accumulation of cholesteryl esters in cultured cells, nor can it account for all of the LDL degraded in vivo and so alternative pathways for LDL catabolism have been sought. Mouse peritoneal macrophages in culture do not take up normal LDL, but express distinct receptors that recognize electronegatively-modified LDL, LDL-dextran sulphate complexes and beta-VLDL. However, the physiological importance of these receptors has not been firmly established. Human monocyte-derived macrophages in culture also express these three receptors, but differ from most cultured cells in that they express LDL receptors when maintained in medium containing serum. Uptake through these LDL receptors has a relatively low affinity for LDL and does not appear to provide a significant amount of the cholesterol required by the cells, a large proportion of which is obtained from endogenous synthesis. Uptake of modified LDL and beta VLDL by macrophages is not tightly controlled and leads to the accumulation of cholesteryl esters in the cell cytoplasm, although these are rapidly lost as free cholesterol if a suitable acceptor is present in the medium. Macrophages have also been shown to synthesize and secrete apoE. Thus it has been postulated that macrophages perform a scavenger function in the arterial wall by clearing damaged or trapped lipoproteins, and prevent cholesterol accumulation by secreting it in a form that can be readily transported back to the liver for excretion. Only when this process becomes overloaded does foam cell formation occur.
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D002788:Cholesterol Esters / Q000097:blood; D004705:Endocytosis; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood; D006952:Hyperlipoproteinemia Type III / Q000097:blood; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D011973:Receptors, LDL / Q000378:metabolism
D002788:Cholesterol Esters; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D002784:Cholesterol