FIGURE 11.
Convergent and divergent signaling events elicited within viable cells in response to the recognition or engulfment of dead cells. The recognition and subsequent engulfment of dead cells by both professional and non-professional phagocytes is coupled with a number of early signaling events. These signaling events can be separated into two categories: those that appear to be conserved among all cell types (A) and those that vary depending upon the cell type (B). A, receptor-mediated discrimination of apoptotic and necrotic corpses elicits directionally opposite responses in proinflammatory transcription (denoted here as NFκB-dependent transcriptional activity) and the activity of the signaling kinases ERK1/2, JNK1/2, p38, and p90RSK. These signaling events are identical between mϕ and kidney proximal tubular epithelial cells (i.e. BU.MPT cells). B, mϕ and kidney proximal tubular epithelial cells differ with respect to the effect of dead cells on the activity of the kinase Akt. For mϕ, Akt activity is linked to phagocytosis, so that engulfment of dead targets, whether apoptotic or necrotic, leads to activation of Akt and subsequent phosphorylation of its downstream targets (including GSK3β and Bad). Phagocytosis of latex beads, which occurs in a receptor-independent manner, similarly leads to activation of Akt. In marked contrast, for kidney proximal tubular epithelial cells, Akt activity is linked to the recognition of dead targets. Receptor-mediated discrimination of apoptotic versus necrotic corpses elicits directionally opposite responses in Akt activity. Although apoptotic corpses inhibit Akt activity, necrotic corpses stimulate Akt activity. Latex particles, which are taken up in a receptor-independent manner, have no effect on Akt activity.