The “Phagocytic Synapse” and Clearance of Apoptotic Cells

Apoptosis and subsequent phagocytic clearance of apoptotic cells is important for embryonic development, maintenance of tissues that require regular cellular renewal and innate immunity. The timely removal of apoptotic cells prevents progression to secondary necrosis and release of cellular contents, preventing cellular stress and inflammation. In addition, altered phagocyte behaviour following apoptotic cell contact and phagocytosis engages an anti-inflammatory phenotype which impacts upon development and progression of inflammatory and immune responses. Defective apoptotic cell clearance underlies the development of a variety of inflammatory and autoimmune diseases. There is considerable functional redundancy in the receptors that mediate apoptotic cell clearance, highlighting the importance of this process in diverse physiological processes. A single phagocyte may utilise multiple receptor pathways for the efficient capture of apoptotic cells by phagocytes (tethering) and the subsequent initiation of signalling events necessary for internalisation. In this review, we will consider the surface alterations and molecular opsonisation events associated with apoptosis that may represent a tunable signal that confers distinct intracellular signalling events and hence specific phagocyte responses in a context-dependent manner. Efficient molecular communication between phagocytes and apoptotic targets may require co-operative receptor utilisation and the establishment of efferocytic synapse which acts to stabilise adhesive interactions and facilitate the organisation of signalling platforms that are necessary for controlling phagocyte responses.