The inhibition of foam cell formation by sodium diethyldithiocarbamate.
A prominent feature of human atherosclerosis is the lipid-laden foamy macrophage, which often also contains the insoluble pigment, ceroid. The culture of macrophage-like cells, P388D1s, with artificial lipoproteins composed of cholesteryl linoleate (CL) and bovine serum albumin (BSA) results in foam cell formation with lipoprotein uptake and the intracellular accumulation of ceroid. Ceroid accumulation is accompanied by the oxidation of the cholesterol ester as monitored by gas chromatography. The sodium salt of diethyldithiocarbamic acid (DDC) at 1-5 microM effectively inhibited lipoprotein uptake, cholesteryl linoleate oxidation and ceroid accumulation in cultures of P388D1. Further studies showed that intracellular ceroid accumulation appeared to require the presence of cystine in the medium. Lipoprotein oxidation by this macrophage-like cell therefore appears to involve a mechanism dependent on cystine metabolism which is consistent with previous reports of macrophage-mediated lipoprotein oxidation. Studies on CL/BSA-induced ceroid accumulation in human monocytes also showed that DDC behaved in much the same manner. This inhibitory effect of DDC on foam cell formation, often considered a primary event of atherosclerosis, at concentrations as low as 1 microM, suggests the need for further, more comprehensive, studies on this compound's activities.
Schultz
D
D
Department of Pathology, University of Cambridge, U.K.
Skamarauskas
J T
JT
Law
N
N
Mitchinson
M J
MJ
Hunt
J V
JV
D000418:Albumins / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002566:Ceroid; D004050:Ditiocarb / Q000494:pharmacology*; D005453:Fluorescence; D005487:Foam Cells / Q000187:drug effects / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008074:Lipoproteins / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology*; D051379:Mice
D000418:Albumins; D002566:Ceroid; D008074:Lipoproteins; D004050:Ditiocarb