Figure 1.

Discrete signaling events elicited within phagocytes by the recognition vs. engulfment of dead cells. The clearance of dead cells by phagocytes, both professional and non-professional, is associated with a number of early signaling events. These signaling events can be broken up into: (A) those mediated by the recognition of apoptotic vs. necrotic corpses, and (B) those mediated by their engulfment via a common phagocytic machinery. (A) Receptor-mediated discrimination of apoptotic vs. necrotic corpses elicits directionally opposite responses in pro-inflammatory transcription (denoted here as NFκB-dependent transcriptional activity) and the activity of the signaling kinases ERK1/2, JNK1/2 and p38. Apoptotic cells, at all stages, irrespective of the integrity of the plasma membrane, initiate identical signaling events. (B) Signaling events linked to the engulfment of apoptotic and necrotic cells are directionally similar and lead to the activation of Akt and its downstream targets, GSK3β and BAD. Latex particles, which are taken up in a receptor-independent manner, elicit no recognition-dependent signaling events, but, like dead cells, activate Akt via their engulfment.