Figure 1.

Cell death clearance processing by phagocytes through finding apoptotic cells, recognition their signals and engulfment of the cell corpses. (A) The “find me” signal: the dying cells release signals such as UTP, ATP, sphingosine-1-phosphate (S1P), and lysophosphatidylcholine or fractalkine through apoptosis. These “find me” signals can also conduct phagocytes to the location of cell death. Phagocytes can thus sense the “find me” signal to detect apoptotic cells using cognate receptors including sphingosine-1-phosphate receptor (S1PRs), purinergic receptors (P2Y2), G-protein-coupled receptor (G2A), and CXCR3. (B) The “eat me” signal: the dying cells expose “eat me” signals on their surface, so phagocytes can recognize and engulf apoptotic cells by recruiting a complex of receptors and bridging molecules. The main common “eat me” signals include the expression of phosphatidylserine (PS) on the outer layer of plasma membrane, brain-specific angiogenesis inhibitor 1, T cell immunoglobulin mucin receptor (TIM1, TIM3, TIM4), RAGE, and stabilin along with PS-specific bridging molecules, Gas6, Milk Fat Globule EGF Factor 8 (MFG-E8), and protein S. Other “eat me” signals include calreticulin (CRT) and ICAM3, which can modulate the identification and engulfment of apoptotic cells by LRP receptors (via C1q) and CD14, respectively. (C) The engulfment process: after recruitment of engulfment receptors through the activity of Rac pathway, the polymerization of actin and rearranging of cytoskeletal are initiated. Although the mechanism of TIM4 in this process is unknown, some engulfment receptors recruit the DOCK180/ELMO1 set (αvβ3, TAM, stabilin-2, and LRP). Thus, disorders during this step can lead to autoimmunity and inflammatory.