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The efficient elimination of apoptotic cells is crucial for tissue homeostasis in multicellular organisms. Secreted “find-me,” exposed “eat-me,” and lacking “don''t-eat-me” signals comprise the central elements of apoptotic cell removal, thus preventing the release of intracellular contents into the surrounding tissue. This is of special importance, as there is growing evidence that the onset of autoimmune disorders can be linked to the inefficient removal of apoptotic cells. This review focuses on the signals displayed by apoptotic cells, the bridging and receptor molecules on the phagocyte, and is intended to present a simplified model of the phagocytic synapse. Additionally, the recent discovery of lysophosphatidylcholine functioning as soluble attraction signal is discussed in the general context of apoptotic cell clearance. [Copyright &y& Elsevier]

Efficient engulfment of the intact cell corpse is a critical end point of apoptosis, required to prevent secondary necrosis and inflammation. The presentation of “eat-me” signals on the dying cell is an important part of this process of recognition and engulfment by professional phagocytes. Here, we present evidence that apoptotic cells secrete chemotactic factor(s) that stimulate the attraction of monocytic cells and primary macrophages. The activation of caspase-3 in the apoptotic cell was found to be required for the release of this chemotactic factor(s). The putative chemoattractant was identified as the phospholipid, lysophosphatidylcholine. Further analysis showed that lysophosphatidylcholine was released from apoptotic cells due to the caspase-3 mediated activation of the calcium-independent phospholipase A2. These data suggest that in addition to eat-me signals, apoptotic cells display attraction signals to ensure the efficient removal of apoptotic cells and prevent postapoptotic necrosis. [Copyright &y& Elsevier]

Summary Apoptosis is an essential form of cell death underlying daily tissue regeneration. In tumor biology, apoptosis resistance is a well-established hallmark of cancer that is targeted by therapeutic approaches. A new study assigns a hitherto-underestimated function to this ‘deadly friend’: apoptotic cells promote tumor growth, accumulation of tumor-associated macrophages, and angiogenesis. [ABSTRACT FROM AUTHOR]

Summary: Extracellular nucleotides have been reported to act as a ‘find-me’ signal in the context of phagocyte recruitment by apoptotically dying cells. A new study now examines the mechanisms of nucleotide release during apoptosis and describes the hemichannel-forming protein pannexin 1 as a crucial player in this scenario. [Copyright &y& Elsevier]

Yeast can undergo cell death accompanied by cellular markers of apoptosis. However, orthologs of classical mammalian apoptosis regulators appeared to be missing from the yeast genome, challenging a common mechanism of yeast and mammalian apoptosis. Here we investigate Yor197w, a yeast protein with structural homology to mammalian caspases, and demonstrate caspase-like processing of the protein. Hydrogen peroxide treatment induces apoptosis together with a caspase-like enzymatic activity in yeast. This response is completely abrogated after disruption and strongly stimulated after overexpression of Yor197w. Yor197w also mediates the death process within chronologically aged cultures, pointing to a physiological role in elimination of overaged cells. We conclude that Yor197w indeed functions as a bona fide caspase in yeast and propose the name Yeast Caspase-1 (YCA1, gene YCA1). [Copyright &y& Elsevier]

Blood platelets are critical for hemostasis and thrombosis and play diverse roles during immune responses. Despite these versatile tasks in mammalian biology, their skills on a cellular level are deemed limited, mainly consisting in rolling, adhesion, and aggregate formation. Here, we identify an unappreciated asset of platelets and show that adherent platelets use adhesion receptors to mechanically probe the adhesive substrate in their local microenvironment. When actomyosin-dependent traction forces overcome substrate resistance, platelets migrate and pile up the adhesive substrate together with any bound particulate material. They use this ability to act as cellular scavengers, scanning the vascular surface for potential invaders and collecting deposited bacteria. Microbe collection by migrating platelets boosts the activity of professional phagocytes, exacerbating inflammatory tissue injury in sepsis. This assigns platelets a central role in innate immune responses and identifies them as potential targets to dampen inflammatory tissue damage in clinical scenarios of severe systemic infection., (Copyright © 2017 Elsevier Inc. All rights reserved.)