[2][3] A leaky membrane leads to secondary necrosis which may cause additional inflammation, therefore, it is best to remove dying cells before this occurs.
[1] A wide range of molecules, from cellular lipids, proteins, peptides, to nucleotides, act as find-me signals.
Mutants that could not carry out normal caspase-mediated apoptosis were used to demonstrate that cells in the beginning stages of death were still efficiently recognized and removed by phagocytes.
This occurred because the engulfment machinery of the phagocytes was still functioning normally even though the apoptotic process in the dying cell was disrupted.
[6] A study done in 2003 showed the breast cancer cells release find me signals known as lysophosphatidylcholine.
[7] This research brought the concept of find-me signals to the fore front of cell clearance research and introduced the idea that dying cells release signals that flow throughout the body's tissues in order to alert and recruit monocytes to their location.
[3] Known types of find-me signals include: All of these molecules are linked to monocyte or macrophage recruitment towards dying cells.
[7] The amount of LPC released is small, so it is unclear how it is able to set up a concentration gradient in the serum or plasma in order to attract phagocytes to their location.
The increased presence of SphK1 is linked to the creation of S1P, which then recruits macrophages to the immediate area surrounding apoptotic cells.
[9] It has also been suggested that S1P kinase 2 (SphK2) is a target of caspase 1, and that a cleaved fragment of SphK2 is what is released from dying cells into the surrounding extracellular space where it is transformed into S1P.
[10] All of the studies thus far characterizing S1P have been done in vitro, and the role or S1P in recruiting phagocytes to apoptotic cells in vivo has not been determined.
[11] CX3CL1 could also be released as part of microparticles from the beginning stages of apoptotic death of Burkitt Lymphoma cells.
[12] Studies were able to show that the controlled release of the nucleotides ATP and UTP from cells in the beginning stages of apoptosis can potentially attract monocytes in vivo and in vitro.
Apoptosis causes a dimerization of S19, inducing a conformation change that allows it to bind to the C5a receptor on monocytes.
Only a fraction of these new cells will stay and become mature, while the rest will die and be cleared by the body's immune system.
Cell damage can occur through environmental factors such as air pollution, UV radiation from the sun, or physical injury.
Find-me signals alert the presence of apoptotic cells to phagocytes when they are in the beginning states of dying.
[18] As long as the engulfment process is functioning and efficient, uncleared apoptotic cells go unnoticed in the body and do not cause any long-term symptoms.
[3] In this case, a dying cell needs to be able to send out an advertisement of sorts to declare its state of death in order to recruit phagocytes to its location.
[3] Phagocytes detect the gradient set up by the find-me signals presented by the dying cell in order to navigate to their location.