LIPID ACCUMULATION AND METABOLISM IN CARRAGEENAN-INDUCED GRANULOMAS COMPARED TO BLOOD MONOCYTES AND THE AORTA

Abstract

Arteries undergoing atherogenic change show an increase in cholesteryl esterifying activity by acylCoA:cholesterol acetyl-transferase (ACAT) and a progressive accumulation of cholesterol esters within monocyte derived foam cells. The study of these factors, however, is limited by the necessity of obtaining artery tissues for analysis. In this study, an in vivo model (Am J Path 118:134 and 120:391, 1985) which permits the analysis of foam cell development without requiring collection of aortas was examined in more detail. New Zealand rabbits (6 each) were either maintained on a 1% cholesterol/peanut oil diet (HD) or a regular chow diet (RD) for 2 weeks after which each had 15 ml of a 1% carra-geenan gel (Marine Colloids) injected subcutaneously into the mid-abdominal area. The rabbits were maintained on their respective diets for an additional 4 weeks. At sacrifice, blood was collected for both serum and monocyte isolation. Granulomas and aortic arches were also excised. Tissues were assayed for lipid accumulation and metabolism. Electron and light microscopy was also performed on immersion fixed (1% glutaraldehyde) granuloma tissue. Granulomas of HD rabbits were pale yellow and averaged 36 grams, while RD granulomas were a pale red and averaged 11 grams (p less than 0.05). RD granulomas did not stain with oil red 0. HD granulomas had homogenous oil red 0 staining which indicated lipid accumulation. Both RD and HD granulomas had large numbers of macrophages. RD macrophages accumulated follicular carrageenan, but not lipid. In HD granulomas, foam cell development was observed. Granuloma lipid content and metabolism paralleled the aorta and blood monocytes. The HD tissue had increased ACAT activity and lipid composition changes indicative of atherosclerosis. RD granulomas had no elevation of lipid content or ACAT activity. The results suggest that the carrageenan-induced granulomas provides a useful model for studying the biochemical and morphologic changes characteristic of aortic monocyte-derived foam cells and the early arterial atherosclerotic process.