Targeting lipoproteins to Fc gamma receptors with bispecific antibodies

Abstract

The data presented here support use of bispecific antibodies (BsAb) for studying the role of each of the different types of IgG Fc receptors (Fc gamma Rs) in uptake and metabolism of low-density lipoprotein (LDL) immune complexes. The bispecific anti-Fc gamma R x anti-LDL antibodies used in these studies were effective in specifically triggering metabolic uptake and degradation of LDL immune complexes (LDL-IC) through each type of Fc gamma R. Using LDL-IC prepared with LDL aggregates, foam cell formation was induced with relatively acute stimulation. Thus, these conditions will be appropriate for studying lipoprotein metabolism in the context of specific Fc gamma R under a variety of conditions to determine if, in fact, there are differences in sterol metabolism associated with the different types of Fc gamma R and for comparing metabolism to that mediated by the other important pathways of lipoprotein uptake (native LDL receptors and scavenger receptors). The results of these studies will reveal which of these pathways are potentially most important in foam cell formation and might suggest the possibility that macrophage foam cell formation could be altered by redirecting LDL to particular pathways.