Voices from the dead: The complex vocabulary and intricate grammar of dead cells.

Abstract

Of the roughly one million cells per second dying throughout the body, the vast majority dies by apoptosis, the predominant form of regulated cell death in higher organisms. Long regarded as mere waste, apoptotic cells are now recognized as playing a prominent and active role in homeostatic maintenance, especially resolution of inflammation, and in the sculpting of tissues during development. The activities associated with apoptotic cells are continually expanding, with more recent studies demonstrating their ability to modulate such vital functions as proliferation, survival, differentiation, metabolism, migration, and angiogenesis. In each case, the role of apoptotic cells is active, exerting their effects via new activities acquired during the apoptotic program. Moreover, the capacity to recognize and respond to apoptotic cells is not limited to professional phagocytes. Most, if not all, cells receive and integrate an array of signals from cells dying in their vicinity. These signals comprise a form of biochemical communication. As reviewed in this chapter, this communication is remarkably sophisticated; each of its three critical steps-encoding, transmission, and decoding of the apoptotic cell's "message"-is endowed with exquisite robustness. Together, the abundance and intricacy of the variables at each step comprise the vocabulary and grammar of the language by which dead cells achieve their post-mortem voice. The combinatorial complexity of the resulting communication network permits dying cells, through the signals they emit and the responses those signals elicit, to partake of an expanded role in homeostasis, acting as both sentinels of environmental change and agents of adaptation.