IgG transport and antigen destruction has been highly studied for the development of antibodies that can improve clearance of targets such as virally infected cells and tumor cells. The binding of antibodies to Fc gamma receptors on macrophages contributes to clearance of antibody-antigen complexes and therefore important for improving antibody design. Here, we show that pre-treatment of macrophages with IgG2a opsonized liposomes leads to antibody recycling capable of priming macrophages for phagocytosis of SRBCs, after IgG2a is removed from the liposomes and recycled to the cell surface. We demonstrate that internalization of antibody opsonized liposomes occurs by a receptor mediated uptake pathway with little contribution from macropinocytosis. However, IgG2a-lipsome complexes are trafficked to the macropinosome membrane where IgG is sorted off liposomes in a pH-dependent fashion and recycled to the cell surface. The segregation process occurs in a sorting compartment associated with the macropinosome, demonstrating that the macropinosome can act as an antibody-antigen sorting nexus. Traffic of liposomes is not predicted by fluid phase movement as delivery of liposomes to the lysosomal compartment is delayed compared to the fluid phase marker Lucifer yellow. Together, these show that the macropinosome may have a novel function in controlling antibody antigen sorting.

Macropinosome organizes sorting and recycling of IgG from the surface of nanoparticles in macrophages

2019 Spring National Meeting

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