Cellular damage in mouse peritoneal macrophages exposed to cholesteryl linoleate.
Mouse peritoneal macrophages readily oxidize cholesteryl linoleate/bovine serum albumin emulsions to produce soluble lipid oxidation products, some of the latter being thought to cause cell damage. Mouse peritoneal macrophages were therefore incubated in the presence of cholesteryl linoleate/bovine serum albumin emulsion with and without the addition of dl-alpha tocopherol. The macrophages were observed morphologically and cell damage was estimated by three methods: trypan blue exclusion, lactate dehydrogenase release and tritiated adenine release. All the methods showed significant cell damage which was reduced in the presence of physiological levels of dl-alpha tocopherol. Cholesteryl oleate/bovine serum albumin, which is taken up by macrophages but is not oxidized, was not toxic. dl-Alpha tocopherol was itself toxic in higher concentrations. This self-inflicted macrophage damage might explain the onset of necrosis in atherosclerotic plaques.
Reid
V C
VC
Department of Pathology, Cambridge, U.K.
Brabbs
C E
CE
Mitchinson
M J
MJ
D000225:Adenine / Q000378:metabolism; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D002788:Cholesterol Esters / Q000378:metabolism / Q000633:toxicity*; D066298:In Vitro Techniques; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D010084:Oxidation-Reduction
D002788:Cholesterol Esters; C021976:cholesteryl linoleate; D000225:Adenine