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Dr Ivan Poon NHMRC Career Development Fellow, Biochemistry

Billions of cells undergo apoptosis (a form of programmed cell death) daily as part of homeostasis in the adult human. It is crucial that free apoptotic cells are readily cleared as the accumulation of apoptotic cells has been linked to numerous disease states such as inflammation, autoimmunity, cancer and infection. Thus, understanding the molecular basis of apoptotic cell removal will provide new avenues for therapeutic intervention.

Efficient removal of apoptotic cells depends on whether phagocyte can successfully locate and subsequently engulf dying cells. To achieve this, apoptotic cells can 'advertise' their presence by releasing chemotactic factors known as 'find-me' signals. Following recruitment, phagocytes can identify apoptotic cells through 'eat-me' signals exposed on the surface of apoptotic cells to trigger engulfment. In general, the recognition of apoptotic cells not only triggers phagocytosis but can also promote an anti-inflammatory response to control inflammation and maintain immunological tolerance.

Prior to the recruitment and recognition by phagocytes, apoptotic cells often undergo a number of distinct morphologic changes. These changes in turn allow an apoptotic cell to be efficiently cleared by phagocytes. For instance, apoptotic cells can disassemble into discrete subcellular membrane-bound particles (1-5 um) known as apoptotic bodies. The generation of these 'bite-size' apoptotic bodies can facilitate their uptake and processing by phagocytes. For many years, apoptotic bodies are thought to be formed simply from membrane blebbing, a process driven by actomyosin contraction. However, the precise molecular machinery that control the quantity and quality of apoptotic bodies is not well defined. We propose that regulated apoptotic bodies formation during cell death is essential for the prompt removal of apoptotic cells. Importantly, modulating the mechanism of apoptotic bodies formation could alter the consequence of corpses clearance in health and diseases.

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