Intimal infiltration of lipid-filled macrophages (Mφs) is an important event in the pathogenesis of atherosclerosis. To better understand Mφ functions, a model for the extravascular in vivo generation of foam cells in rat peritoneal cavities was utilized. Morphologic alterations, intracellular cholesterol accumulation, subpopulation, activation and proliferative properties of Mφs from hypercholesterolemic rats (HMφs) were compared with Mφs from normal rats (NMφs). HMφs revealed a significant increase of cholesterol mass in the cytoplasm; 65% of HMφs were loaded with various amounts of oil-red-O-stainable lipid droplets which were barely identified in NMφs. Ultrastructurally, accumulated lipid droplets in HMφs were either membrane-bound or membrane-free in the cytoplasm. Further biochemical analysis revealed that cellular levels of total cholesterol, free cholesterol, and cholesteryl esters in HMφs were increased 6-, 8-, and 4-fold, respectively. As to the Mφ subpopulation, there was a significant increase of Ia-antigen-positive cells in HMφs (15.8 vs. 8.8%), indicating that these cells were in a state of activation. To investigate the mitotic activity, the proliferative potential of Mφs was determined both in vivo and in vitro using monoclonal anti-bromodeoxyuridine (anti-BrdU) antibody to dectect BrdU incorporated into cell DNA. However, both NMφs and HMφs showed little proliferation; proliferative indices were less than 2%. This implies that Mφs are barely replicating, and hypercholesterolemia does not stimulate Mφs in this aspect. We conclude that hypercholesterolemia leads to a rapid accumulation of lipids in Mφs, which may be associated with Mφ activation. Such alterations of Mφ functions induced by dietary cholesterol may be potentially important in the development of the fatty streak formation.

Keywords:
Macrophages, Atherosclerosis, Hypercholesterolemia, Foam cells
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© 1994 S. Karger AG, Basel
1994
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