Table 1.

Phagocytosis-related signals on the surface of apoptotic cells

Types of signal	Molecules	Type of specimen	Mechanism	Reference
“Find me” signal	LPC	MCF-7 breast cancer cells	IPLA2, upon cleavage by caspase, facilitates the release of LPCs in dying cells, promoting monocyte recruitment.	[155]
	S1P	Jurkat and U937 leukemia cells	Apoptosis stimulation leads to SphK1 elevation, which is linked to S1P production, which recruits macrophages to the site of apoptotic cells.	[156]
	CX3CL1	Burkitt Lymphoma cells	The soluble chemokine fragment of fractalkine, which is typically located on the plasma membrane and acts as an intercellular adhesion molecule, is released as a 60 kDa fragment during apoptosis and can act as a chemoattractant.	[157]
	The nucleotides ATP and UTP	Jurkat cells, primary thymocytes, MCF-7 cells, lung epithelial cells	Early apoptotic cells release the nucleotides ATP and UTP via PANX1, which are then induced by P2Y2 on monocytes, resulting in a “find me” signal that attracts monocytes.	[158]
“Eat me” signal	PtdSer	Many different cell types	The two recognition modes of PtdSer include direct recognition by phagocytic receptors (e.g., TIM-4) and indirect recognition, in which bridging molecules (e.g., MFG-E8) bind to PtdSer, which is recognized by membrane proteins. Thus, PtdSer mediates the structural rearrangement of phagocytic cells’ cytoskeleton to make cadaveric uptake easier.	[159]
	ICAM-1	Many different cell types	Alteration in ICAM-1 epitopes on the cell surface leads to the release of an “eat me” signal.	[160]
	CRT	Murine CT26 colon cancer cells	When cells die due to ER stress, eIF2α is phosphorylated by activated protein kinase RNA-like ER kinase, causing CRT to translocate from the ER to the cell surface. The phagocytes’ low-density lipoprotein receptor-related protein (CD91) detects this and absorbs the cells.	[161,162]

Abbreviations: LPC, Lipid lysophosphatidylcholine; MCF-7, Michigan cancer foundaion-7; iPLA2, Calcium-independent phospholipase A2; S1P, Sphingosine 1-phosphate; SphK1, S1P kinase 1; CX3CL1, Fractalkine; ATP, Adenosine triphosphate; UTP, Uridine triphosphate; PANX1, Pannexin 1; PtdSer, Phosphatidylserine; TIM-4, T cell immunoglobulin and mucin-domain-containing molecule 4; MFG-E8, Milk fat globule-epidermal growth factor (EGF) factor 8; ICAM-1, Intercellular adhesion molecule-1; CRT, Calreticulin; ER, Endoplasmic reticulum.