Scent of dying cells: The role of attraction signals in the clearance of apoptotic cells and its immunological consequences

In multicellular organisms apoptotic cells are rapidly and efficiently removed by professional or semi-professional phagocytes. The molecular mechanisms and the key players involved in this highly coordinate process, as well as its immunological outcome constitute a vividly expanding field of scientific interest. A plethora of studies provided a detailed understanding of the interaction site between the dying cell and the phagocyte, as well as to the current concept that apoptotic cell removal leads to a non- or anti-inflammatory response, whereas necrotic cell removal stimulates a pro-inflammatory reaction. In contrast, our current knowledge about the soluble factors released from apoptotic cells is rather limited, although meanwhile it is generally accepted that not only the dying cell itself but also the substances, which are liberated during cell death, contribute to the process of corpse clearance and the subsequent immune response. This review is intended to summarize the up-to-date knowledge about apoptotic cell-derived attraction signals, their function as phagocytic chemoattractants, their influence on the immune system, and the receptors, which are engaged in this scenario. (C) 2009 Elsevier B.V. All rights reserved.