Figure 2.

Recognition of red blood cells’ biochemical integrity by iron-recycling macrophages. Aged/injured erythrocytes expose exoplasmic phosphatidylserine (PS) on their surface and become opsonized by naturally occurring antibodies (NAbs). Among the cognate receptors for these senescence signals that are expressed on RPMs and KCs, TAM receptors AXL and MERTK, TIM4 and Fc receptor CD16 are the most abundant. A “don’t eat me” signal that prevents the clearance of young and intact erythrocytes is provided by the interaction between SIRPα at the surface of the macrophage with CD47 expressed by erythrocytes.