Evidence of dual pathways for lipid uptake during chylomicron remnant-like particle processing by human macrophages.
BACKGROUND
Though it is now clear that chylomicron remnants are pro-atherogenic lipoproteins, events leading to their incorporation by macrophages are poorly understood.


METHODS
This study investigates, in human macrophages, the fate of either [(3)H]cholesteryl oleate or [(3)H]triacylglycerol carried by human apolipoprotein-E-containing chylomicron remnant-like particles (CRLP) and the influence of CRLP containing trilinolein, (18:2)CRLP, or triolein, (18:1)CRLP, on lipid accumulation, newly synthesized cholesteryl ester (CE) and triacylglycerol (TG).


RESULTS
Labelled fatty acids from TG were markedly incorporated into TG and phospholipid and, to a lesser extent, into free fatty acids and were scarcely recovered in cholesteryl esters. [(3)H]CE from CRLP accumulated in cells in a dose-dependent manner with a significant difference between concentrations of 10 and 40 microg cholesterol/ml with (18:2)CRLP. In the same concentration range, TG synthesis was enhanced by about 46 and 30% by (18:2)CRLP and (18:1)CRLP cholesterol, respectively, whereas the esterification of cholesterol, evaluated by [(3)H]oleate incorporation, was decreased by about 30% with both types of CRLP. Endocytosis inhibition did not prevent cell cholesterol and TG accumulation, whereas lipoprotein lipase inhibition reduced the TG content.


CONCLUSIONS
The results are consistent with the hypotheses that in macrophages dietary remnants may support TG and CE internalization via different mechanisms. Extracellular lipolysis seems particularly important for internalization of dietary fatty acids, whereas the entrance of CE seems attributable to a concomitant selective CE uptake mediated by scavenger receptor class B type I, since the scavenger receptor class B type I antibody induces significant inhibition (38%) of [(3)H]CE transported by CRLP, but does not affect internalization of [(3)H]TG carried by the same particles.
Napolitano
Mariarosaria
M
Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Bravo
Elena
E
D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E / Q000032:analysis; D001692:Biological Transport; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000032:analysis / Q000378:metabolism*; D053298:Chylomicron Remnants; D002914:Chylomicrons / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D000077403:Orlistat; D010316:Particle Size; D010743:Phospholipids / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000276:immunology / Q000378:metabolism; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism*; D014316:Tritium
D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D002788:Cholesterol Esters; D053298:Chylomicron Remnants; D002914:Chylomicrons; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D007783:Lactones; D010743:Phospholipids; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; D014316:Tritium; C014409:cholesteryl oleate; D000077403:Orlistat; D008071:Lipoprotein Lipase