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. T he culture of macrophage-like cells, P388D(1)s, with artificial lipopr oteins 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 accompani ed by the oxidation of the cholesterol ester as monitored by gas chrom atography. The sodium salt of diethyldithio-carbamic acid (DDC) at 1-5 mu M effectively inhibited lipoprotein uptake, cholesteryl linoleate oxidation and ceroid accumulation in cultures of P388D(1). Further stu dies 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 dependen t on cystine metabolism which is consistent with previous reports of m acrophage-mediated lipoprotein oxidation. Studies on CL/BSA-induced ce roid accumulation in human monocytes also showed that DDC behaved in m uch the same manner. This inhibitory effect of DDC on foam cell format ion, often considered a primary event of atherosclerosis, at concentra tions as low as 1 mu M, suggests the need for further, more comprehens ive, studies on this compound's activities.