FIGURE 2.

Effects of hemolysis on the monocyte/macrophage compartment. Heme affects phagocytic activity of macrophages and microbial clearance by directly activating the DOCT8/Cdc42 signaling pathway, and inhibiting cytoskeletal remodeling necessary for phagocytosis. In addition, heme induces monocyte differentiate into red pulp macrophages through BACH1 degradation and activation of SPIC signaling, thus restoring iron recirculation needed for replenishing red cells in hemolytic conditions. In addition, heme induces heme oxygenase 1 expression in nonclassical monocytes which in turn drive the expansion of Tregs, perhaps further contributing to impaired adaptive immune response in hemolytic conditions. Tregs, regulatory T cells. SPIC, spleen focus forming virus proviral integration-site.