IGE-DEPENDENT GENERATION OF FOAM CELLS - AN IMMUNE MECHANISM INVOLVING DEGRANULATION OF SENSITIZED MAST-CELLS WITH RESULTANT UPTAKE OF LDL BY MACROPHAGES

Because a role has been suggested for IgE in cardiovascular diseases a nd for mast cells in cholesterol accumulation within the macrophages o f atherosclerotic lesions, we examined mast cell-macrophage interactio ns in vitro by using rats with high serum levels of IgE antibodies. Th e rats were immunized with an antigen (ovalbumin) and adjuvant (Bordet ella pertussis vaccine) to provoke synthesis of IgE and to sensitize t heir 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 i mmunized rats, the mast cells responded by exocytosing their heparin-p roteoglycan-containing granules. When IgE-bearing peritoneal mast cell s were cocultured with peritoneal macrophages (also from the immunized rats) in a medium enriched in LDL, addition of ovalbumin to the incub ation medium triggered a dose-dependent release of granules and a dose -dependent increase in the rate of LDL uptake by the macrophages. In c ontrast, ovalbumin had no effect on LDL uptake if the cultures contain ed only macrophages or if the mast cells and macrophages were from non immunized rats. Thus, the sequence of events leading to enhanced uptak e of LDL by macrophages depended wholly on IgE-dependent degranulation of the sensitized mast cells. With the aid of gold-labeled LDL we dem onstrated that the exocytosed mast cell granules had bound LDL particl es and carried them into the macrophages, with subsequent formation of foam cells. The current series of experiments delineates a novel immu nologic mechanism for the formation of macrophage foam cells and assig ns a potentially atherogenic role to mast cell-bound IgE antibodies.