Lipid metabolism in the inflammatory lesion of a mouse model of delayed type hypersensitivity. I. Increased acylCoA:cholesterol acyltransferase activity as an integral component of the inflammatory response.
Lipid metabolism was studied in a normal model of delayed type hypersensitivity to methylated bovine serum albumin (MBSA). Following initial sensitization to a single injection of MBSA, MBSA-soaked millipore filter disks (10 mm diam) were implanted in subcutaneous pockets and the course of development and the resolution of the inflammatory lesions were followed biochemically for 35 days. Of particular interest were our observations that the activity of the cholesterol esterifying enzyme, which is attributed to acyl-CoA:cholesterol acyltransferase (ACAT; EC 2.3.1.26) was increased up to 38-fold in the developing inflammatory lesion and represented the single most dramatic alteration in lipid metabolism to occur. As the lesions began to show histological evidence of resolving (between 21 and 35 days), ACAT activity declined toward basal levels. The data suggest the possibility that the ACAT reaction is an important component of the inflammatory response and, as such, offers the possibility of a novel approach to controlling the inflammatory process through ACAT inhibition.
Bell
F P
FP
Metabolic Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Dunn
C J
CJ
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D004075:Diglycerides / Q000378:metabolism; D004195:Disease Models, Animal; D004342:Drug Hypersensitivity; D004952:Esters / Q000378:metabolism; D005260:Female; D006099:Granuloma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007267:Injections; D050356:Lipid Metabolism; D051379:Mice; D009132:Muscles / Q000378:metabolism; D009829:Oleic Acids / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000494:pharmacology; D012867:Skin / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D000214:Acyl Coenzyme A; D002250:Carbon Radioisotopes; D004075:Diglycerides; D004952:Esters; D009829:Oleic Acids; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine; D002785:Sterol O-Acyltransferase