Alterations in the functional characteristics of macrophages induced by hypercholesterolemia

Intimal accumulation of monocyte-derived lipid-filled macrophages is an important early event in diet-induced hypercholesterolemia. To better understand the functional alterations in macrophages in hypercholesterolemia, we determined several variables in rat peritoneal macrophages putatively associated with atherogenesis including adhesion to, spreading and locomotion on an endothelial monolayer, migration and phagocytic capacities, and superoxide anion (O2-) production. Compared with macrophages from normal rats (NM0s), macrophages from hypercholesterolemic rats (HM0s) revealed a higher rate of adherence to endothelial cells (ECs) and plastic with more extensive cytoplasmic spreading. Towards a chemoattractant of zymosan-activated serum, HM0s exhibited greater chemotactic migration and more prominent aggregation than NM0s. A computerized film analysis using time-lapse cinemicrophotography disclosed that HM0s moved faster on ECs; the average speed of HM0s was almost twice that of NM0s. HM0 phagocytic activity of fluorescent latex beads was significantly heightened (P less than 0.01). By contrast, there was no significant difference in O2- production between the two groups. These results indicate that hypercholesterolemia may initiate and accelerate the atherosclerotic process, at least in part, by modifying a number of functional properties of macrophages.