Engulfment signals and the phagocytic machinery for apoptotic cell clearance

The clearance of apoptotic cells is an essential process for tissue homeostasis. To this end, cells undergoing apoptosis must display engulfment signals, such as ‘find-me’ and ‘eat-me’ signals. Engulfment signals are recognized by multiple types of phagocytic machinery in phagocytes, leading to prompt clearance of apoptotic cells. In addition, apoptotic cells and phagocytes release tolerogenic signals to reduce immune responses against apoptotic cell-derived self-antigens. Here we discuss recent advances in our knowledge of engulfment signals, the phagocytic machinery and the signal transduction pathways for apoptotic cell engulfment. Programmed cell death and degradation – vital for maintaining healthy multicellular life – depend on several molecular signaling systems. In-San Kim at the Korea Institute of Science and Technology and Seung-Yoon Park at Dongguk University, South Korea, review recent advances in this field. They discuss insights into the processes initiated by what are called “find-me” and “eat-me” signals displayed by cells marked out for destruction. These signals recruit into action the “phagocyte” cells that circulate through the body and engulf and digest the cells that need to die. Defects in these natural maintenance processes have been linked to many common and serious conditions, including autoimmune diseases, chronic obstructive pulmonary disease, atherosclerosis, Alzheimer's disease, and cancer. Fully understanding the signals and activities sending cells to a timely death could lead to new treatments for such conditions.