Comparison of lipid accumulation and metabolism in carrageenan-induced granulomas to aorta and blood monocytes of normal and cholesterol-fed rabbits.
New Zealand rabbits (six each) were either maintained on a standard chow diet (ND) or the chow diet supplemented with cholesterol/peanut oil (HD) for 2 weeks. After 2 weeks, each animal had 15 ml of a 1% carrageenan gel injected subcutaneously into the midabdominal area. Rabbits were maintained on the diets for an additional 4 weeks. At sacrifice, blood was collected both for serum and for monocyte isolation and granulomas and aorta were excised. Tissues were assayed for lipid composition and lipid metabolism. Electron and light microscopies were performed on granuloma tissue. Granulomas from ND animals did not stain with oil red O. Granulomas from HD animals had homogenous oil red O staining indicating lipid accumulation. Granulomas from both ND and HD animals consisted of macrophages. Macrophages from ND rabbits accumulated follicular carrageenan but not lipid, while HD macrophages had the appearance of foam cells. Granuloma lipid content and metabolism closely paralleled the aorta and blood monocytes. The HD tissue had increased acylCoA:cholesterol acetyltransferase (ACAT) activity and lipid composition changes reflective of the atherosclerotic process. ND granulomas had no elevation of lipid content or ACAT. The carrageenan-induced granulomas provide a useful model for studying the biochemical and morphologic changes characteristic of arteries undergoing atherogenic change.
Bell
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Metabolic Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Schaub
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D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000648:ultrastructure; D002351:Carrageenan; D002791:Cholesterol, Dietary / Q000378:metabolism*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D006099:Granuloma / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D008264:Macrophages / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009000:Monocytes / Q000378:metabolism*; D011817:Rabbits
D002791:Cholesterol, Dietary; D002351:Carrageenan