IgE-Dependent Generation of Foam Cells: An Immune Mechanism Involving Degranulation of Sensitized Mast Cells With Resultant Uptake of LDL by Macrophages

Abstract

Abstract Because a role has been suggested for IgE in cardiovascular diseases and for mast cells in cholesterol accumulation within the macrophages of atherosclerotic lesions, we examined mast cell–macrophage interactions in vitro by using rats with high serum levels of IgE antibodies. The rats were immunized with an antigen (ovalbumin) and adjuvant ( Bordetella pertussis vaccine) to provoke synthesis of IgE and to sensitize their mast cells, ie, to allow the IgE to bind to the high-affinity IgE receptors on the mast cell surfaces. On addition of the ovalbumin to suspensions of mast cells isolated from the peritoneal cavity of the immunized rats, the mast cells responded by exocytosing their heparin-proteoglycan–containing granules. When IgE-bearing peritoneal mast cells were cocultured with peritoneal macrophages (also from the immunized rats) in a medium enriched in LDL, addition of ovalbumin to the incubation medium triggered a dose-dependent release of granules and a dose-dependent increase in the rate of LDL uptake by the macrophages. In contrast, ovalbumin had no effect on LDL uptake if the cultures contained only macrophages or if the mast cells and macrophages were from nonimmunized rats. Thus, the sequence of events leading to enhanced uptake of LDL by macrophages depended wholly on IgE-dependent degranulation of the sensitized mast cells. With the aid of gold-labeled LDL we demonstrated that the exocytosed mast cell granules had bound LDL particles and carried them into the macrophages, with subsequent formation of foam cells. The current series of experiments delineates a novel immunologic mechanism for the formation of macrophage foam cells and assigns a potentially atherogenic role to mast cell–bound IgE antibodies.