The attractive signal for phagocytes was identified as lysophosphatidylcholine (LPC), a hydrolysis product of a plasma membrane phospholipid. LPC was released from apoptotic cells of various types via caspase-3–mediated activation of the calcium-independent form of phospholipase A2 (iPLA2). Inhibition of either caspase-3 or iPLA2 blocked chemotaxis of macrophages in vitro. The group also showed that culture supernatants of apoptotic cells injected under the skin of mice caused macrophages to invade the injected area.
The phagocyte side of the story has yet to be worked out. For instance, it is not clear which receptors recognize LPC. Possibilities include G-protein–coupled receptors such as G2A, which binds to LPC and stimulates migration of blood cells. ▪