Sequestration of aggregated low-density lipoproteins by macrophages.
OBJECTIVE
Evidence suggests that much of the LDL in atherosclerotic plaques is aggregated. Aggregation of LDL could be an important factor that determines how this lipoprotein is metabolized by plaque macrophages and the fate of aggregated LDL cholesterol within plaques. This review discusses a novel endocytic pathway by which macrophages process aggregated LDL.


RESULTS
Recently, it has been shown that aggregated LDL can be sequestered in macrophage surface-connected compartments and plasma membrane invaginations by a process termed patocytosis. In contrast to rapid degradation of LDL and aggregated LDL taken up by macrophages through pinocytosis and phagocytosis, respectively, aggregated LDL sequestered in macrophages undergoes only limited degradation. Macrophages can disaggregate and release sequestered aggregated LDL by activating plasminogen to plasmin. Plasmin degrades LDL apolipoprotein B sufficiently to disaggregate the aggregated LDL, releasing it from the macrophage surface-connected compartments. In contrast, activating macrophages with phorbol-myristate-acetate stimulates degradation of aggregated LDL and inhibits plasminogen-mediated release of the aggregated lipoprotein from macrophage surface-connected compartments.


CONCLUSIONS
Macrophage sequestration of aggregated LDL is a unique endocytic pathway relevant not only to the processing of aggregated LDL in atherosclerotic plaques but also for the processing of other materials, such as hydrophobic particles that trigger this endocytic pathway. Macrophage sequestration of aggregated LDL can result in different fates for the aggregated LDL, depending on the state of macrophage activation and the functioning of the plasminogen-based fibrinolytic system. Patocytosis of aggregated LDL should be considered in addition to phagocytosis as a possible uptake pathway in studies of macrophage processing of aggregated LDL.
D001161:Arteriosclerosis / Q000473:pathology*; D002451:Cell Compartmentation; D004705:Endocytosis; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D010587:Phagocytosis
D008077:Lipoproteins, LDL