EVOLUTION OF FOAM CELLS IN SUBCUTANEOUS RABBIT CARRAGEENAN GRANULOMAS .1. LIGHT-MICROSCOPIC AND ULTRASTRUCTURAL-STUDY

  • 1 January 1985
    • journal article
    • research article
    • Vol. 118  (1) , 134-150
Abstract
With an increasing interest in the role of the monocytemacrophage in the pathogenesis of atherosclerosis and as a progenitor of plaque intimal foam cells, a model for the study of foam-cell differentiation in an extravascular environment was developed. Granulomas were induced in 25 normocholesterolemic (NC) and 28 hypercholesterolemic (HC) rabbits by the s.c. injection of 15 ml of 1% carrageenan. Granuloma tissue was harvested at 4, 7, 14 and 28 days and studied by light and transmission electron microscopy. Macrophages and foam cells were isolated by enzymic dispersion with collagenase and cultured for further characterization by scanning electron microscopy, nonspecific esterase (NSE) and oil red O (ORO) staining. Granuloma macrophages from NC rabbits were consistently ORO-negative, contrasting with those from HC rabbits which were strongly ORO-positive, even at 4 and 7 days. With an increasing duration of exposure to hypercholesterolemia, macrophages accumulated increasing amounts of stainable lipid, and in the 28-day HC granulomas, large foam cells distended by lipid inclusions accounted for 70% of the cells present. This model has established that NSE-positive macrophages in HC granulomas accumulate lipid and assume the morphologic characteristics of atheromatous intimal foam cells.