Fig. 2.

Steps during phagocytosis of apoptotic cells. When a cell initiates the apoptotic program, it releases soluble ‘find-me’ signals that attract phagocytes. The apoptotic cell is distinguished from the nearby living cell via the exposure of ‘eat-me’ signals, the most prominent of which is the phosphatidylserine (PtdSer). Eat-me signals are recognized by different engulfment receptors on the phagocytes, resulting in signaling events that facilitate the apoptotic corpse uptake. Engulfment also elicits the transcriptional up-regulation of the cholesterol efflux transporter ABCA1, and increased expression of engulfment receptors. Within the mitochondria, the levels of the uncoupling protein UCP2 are increased, enabling the continued uptake of apoptotic corpses. Anti-inflammatory mediators are expressed and secreted, contributing to tissue homeostasis and inhibition of local inflammation. PtdSer, phosphatidylserine; P2Y2, purinergic P2 receptor Y2; CX3CR1, CX3C chemokine receptor-1; G2A, G protein-coupled receptor G2A; S1PR, sphingosine-1-phosphate receptor; ATP, adenosine triphosphate; UTP, uridine triphosphate; CX3CL1, chemokine (C-X3-C motif) ligand-1, also known as Fractalkine; LPC, lysophosphatydilcholine; S1P, sphingosine-1-phosphate; LXR, liver X receptor; RXR, retinoid X receptor; PPAR, peroxisome proliferator activated receptor; BAI1, brain angiogenesis inhibitor-1; TIM4, T cell immunoglobulin and mucin domain containing molecule-4; RAGE, receptor for advanced glycation end products; TREM-2, triggering receptor expressed on myeloid cells-2; TAM, Tyro Axl Mer family receptor; LRP1, low density lipoprotein receptor related protein-1; SCARF-1 is also known as SREC-1, scavenger receptor expressed by endothelial cell-1; Gas6, growth arrest specific-6; MFG-E8, milk fat globule EGF factor-8; TSP1, thrombospondin-1; ICAM3, intracelullar adhesion molecule-3; CRT, calreticulin.