Proposed molecular mechanism by which HRG enhances the uptake of necrotic cells, but not viable cells, by phagocytes. HRG can simultaneously bind to exposed cellular lipids on necrotic cells and soluble human IgG (in particular IgG2κ) and, consequently, enhance the uptake of necrotic cells by phagocytes via a FcγR-dependent mechanism. This HRG^P-mediated uptake of necrotic cells induces the release of proinflammatory cytokines, such as TNF and IL-8, from phagocytes. In contrast, only free HRG, and not HRG-IgG complexes, is able to bind to heparan sulfate proteoglycans (HSPG) on the surface of viable cells, and this prevents HRG-mediated phagocytosis of viable cells.