E-LDL and Ox-LDL differentially regulate ceramide and cholesterol raft microdomains in human Macrophages.
Atherosclerosis is characterized by the generation of lipid-loaded macrophage-derived foam cells. To study the effect of different types of atherogenic lipoproteins, human macrophages were loaded with enzymatically degraded low density lipoprotein (E-LDL) or oxidized LDL (Ox-LDL). Cellular cholesterol content was increased by E-LDL, whereas Ox-LDL increased the ceramide content. Cell surface expression analysis by flow cytometry and confocal microscopy revealed that Ox-LDL increased ceramide and lactosylceramide expression compared to E-LDL loading and induced ceramide rafts, whereas loading with E-LDL induced cholesterol-rich microdomains. Formation of different rafts may have consequences for raft associated signaling in cholesterol homeostasis and apoptosis in human macrophages.
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, 93042 Regensburg, Germany.
Margot
M
Grandl
Salim Maa
SM
Bared
Gerhard
G
Liebisch
Tobias
T
Werner
Stefan
S
Barlage
Gerd
G
Schmitz
D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002518:Ceramides / Q000032:analysis / Q000378:metabolism*; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007790:Lactosylceramides / Q000032:analysis / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008563:Membrane Lipids / Q000032:analysis / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D015703:Antigens, CD; D002518:Ceramides; D007790:Lactosylceramides; D008077:Lipoproteins, LDL; D008563:Membrane Lipids; C099252:oxidized low density lipoprotein; C009744:CDw17 antigen; D016173:Macrophage Colony-Stimulating Factor; D002784:Cholesterol