The Sound of Silence: Signaling by Apoptotic Cells

Abstract

Apoptosis is a carefully choreographed process of cellular self-destruction in the absence of inflammation. During the death process, apoptotic cells actively communicate with their environment, signaling to both their immediate neighbors as well as distant sentinels. Some of these signals direct the anti-inflammatory immune response, instructing specific subsets of phagocytes to participate in the limited and careful clearance of dying cellular debris. These immunomodulatory signals can also regulate the activation state of the engulfing phagocytes. Other signals derived from apoptotic cells contribute to tissue growth control with the common goal of maintaining tissue integrity. Derangements in these growth control signals during prolonged apoptosis can lead to excessive cell loss or proliferation. Here, we highlight some of the most intriguing signals produced by apoptotic cells during the course of normal development as well as during physiological disturbances such as atherosclerosis and cancer.

Keywords: Apoptosis-induced apoptosis; Apoptosis-induced proliferation; Apoptotic bodies; Caspases; Fractalkine; Mahakali effect; Phoenix Rising; Phosphatidylserine.

Figure 1

Apoptotic cells communicate with phagocytes to modulate immune responses to cell death. Apoptotic cells communicate with professional phagocytes such as macrophages and nonprofessional phagocytes such as engulfing epithelial cells. The apoptosis-derived signals include (1) soluable chemokines, (2) membrane-bound proteins and phospholipids, and (3) apoptotic microblebs. These signals are capable of directing appropriate anti-inflammatory responses promoting survival of neighboring healthy tissue.

Figure 2

Apoptotic cells direct growth control. Apoptotic cells can produce a variety of signals that can have an effect on the growth state of the surviving tissue. The outcome of this communication can depend on both the amounts of signal produced and the receptivity of the surviving cell to these different stimuli.