Dying cells say come-hither

Apoptotic cells are swallowed whole by phagocytes before they can release intracellular molecules that might produce inflammatory responses. Phagocytes get their instructions from cell surface markers on the dying cells. But in an entire organism the chances that the scavengers will encounter a dying cell in time are low. In a recent report, Kirsten Lauber, Sebastian Wesselborg (University of Tübingen, Tübingen, Germany), and colleagues show that apoptotic cells ensure their discovery by sending a long-distance chemotactic message to phagocytes. The new discovery reveals an additional signaling pathway that may be impaired in patients with autoimmune diseases.

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. ▪

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