Apoptosis induces expression of sphingosine kinase 1 to release sphingosine‐1‐phosphate as a “come‐and‐get‐me” signal

Gude, David; Alvarez, Sergio E.; Paugh, Steven W.; Mitra, Prasenjit; Yu, Jin‐Chen; Griffiths, Rachael; Barbour, Suzanne E.; Milstien, Sheldon; Spiegel, Sarah

doi:10.1096/fj.08-107169

Cited by 316 publications

(259 citation statements)

References 56 publications

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“…However, it is important to note that it was never directly shown that S1P from the apoptotic supernatants was the chemotactic factor. In addition, the authors showed that there was no increase in extracellular SphK1, 33 suggesting that the S1P generation occurred within a cell. However, they did not rule out any actions of SphK2 as it has since been shown to be secreted during apoptosis in a caspase-dependent manner, possibly leading to extracellular generation of S1P.…”

Section: Steps Involved In Clearancementioning

confidence: 98%

“…It had already been shown that apoptotic cells can release S1P, 32 but its function as a lipid-attraction signal during cell death was not reported until 2008. Gude et al 33 suggested that sphingosine kinase 1 (SphK1) was upregulated during apoptosis and, in turn, led to the increased secretion of S1P. Concomitantly, purified S1P was able to induce phagocyte chemotaxis.…”

Section: Steps Involved In Clearancementioning

confidence: 99%

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Do not let death do us part: ‘find-me’ signals in communication between dying cells and the phagocytes

2016

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The turnover and clearance of cells is an essential process that is part of many physiological and pathological processes. Improper or deficient clearance of apoptotic cells can lead to excessive inflammation and autoimmune disease. The steps involved in cell clearance include: migration of the phagocyte toward the proximity of the dying cells, specific recognition and internalization of the dying cell, and degradation of the corpse. The ability of phagocytes to recognize and react to dying cells to perform efficient and immunologically silent engulfment has been well-characterized in vitro and in vivo. However, how apoptotic cells themselves initiate the corpse removal and also influence the cells within the neighboring environment during clearance was less understood. Recent exciting observations suggest that apoptotic cells can attract phagocytes through the regulated release of 'find-me' signals. More recent studies also suggest that these find-me signals can have additional roles outside of phagocyte attraction to help orchestrate engulfment. This review will discuss our current understanding of the different find-me signals released by apoptotic cells, how they may be relevant in vivo, and their additional roles in facilitating engulfment.

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Section: Steps Involved In Clearancementioning

confidence: 98%

Section: Steps Involved In Clearancementioning

confidence: 99%

Do not let death do us part: ‘find-me’ signals in communication between dying cells and the phagocytes

2016

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“…Considering that AC release S1P (Weigert et al, 2006;Gude et al, 2008) and the further notion that S1P potentially causes HO-1 expression (Man et al, 2005), we assumed that S1P in AC-CM was responsible for HO-1 expression in macrophages. To verify this hypothesis, we stimulated primary human macrophages with authentic S1P for 24 h ( Figure 2A).…”

Section: S1p In Ac-cm Is Crucial In Provoking Ho-1 Inductionmentioning

confidence: 99%

Heme Oxygenase-1 Contributes to an Alternative Macrophage Activation Profile Induced by Apoptotic Cell Supernatants

Weis

Weigert

Knethen

et al. 2009

MBoC

152

128

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Apoptotic cells (AC) are rapidly engulfed by professional phagocytes such as macrophages to avoid secondary necrosis and thus inflammation. Recognition of AC polarizes macrophages toward an anti-inflammatory phenotype, which shows homology to an alternatively activated M2 macrophage. However, mechanistic details provoking these phenotype alterations are incompletely understood. Here, we demonstrate a biphasic up-regulation of heme oxygenase-1 (HO-1), a protein that bears an antiapoptotic as well as an anti-inflammatory potential, in primary human macrophages, which were exposed to the supernatant of AC. Although the first phase of HO-1 induction at 6 h was accomplished by AC-derived sphingosine-1-phosphate (S1P) acting via S1P receptor 1, the second wave of HO-1 induction at 24 h was attributed to autocrine signaling of vascular endothelial growth factor A (VEGFA), whose expression and release were facilitated by S1P. Whereas VEGFA release from macrophages was signal transducer and activator of transcription (STAT) 1-dependent, vascular endothelial growth factor itself triggered STAT1/STAT3 heterodimer formation, which bound to and activated the HO-1 promoter. Knockdown of HO-1 proved its relevance in facilitating enhanced expression of the antiapoptotic proteins Bcl-2 and Bcl-X L , as well as the anti-inflammatory adenosine receptor A 2A . These findings suggest that HO-1, which is induced by AC-derived S1P, is critically involved in macrophage polarization toward an M2 phenotype.

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“…42 Adding methylpyruvate stimulates ATP production and restores the externalization of phosphatidylserine in autophagy-defective cells, suggesting that autophagy maintains the level of ATP under these conditions. 42 Interestingly sphingosine 1-phosphate, which is known to stimulate autophagy, 43 is secreted by dying cells 44 and has been identified as a 'come and get me' signal. These findings highlight the importance of autophagy in ensuring a clean death process by favoring the elimination of apoptotic bodies.…”

Section: Autophagy and Apoptosismentioning

confidence: 99%

Does autophagy have a license to kill mammalian cells?

et al. 2008

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Macroautophagy is an evolutionarily conserved vacuolar, self-digesting mechanism for cellular components, which end up in the lysosomal compartment. In mammalian cells, macroautophagy is cytoprotective, and protects the cells against the accumulation of damaged organelles or protein aggregates, the loss of interaction with the extracellular matrix, and the toxicity of cancer therapies. During periods of nutrient starvation, stimulating macroautophagy provides the fuel required to maintain an active metabolism and the production of ATP. Macroautophagy can inhibit the induction of several forms of cell death, such as apoptosis and necrosis. However, it can also be part of the cascades of events that lead to cell death, either by collaborating with other cell death mechanisms or by causing cell death on its own. Loss of the regulation of bulk macroautophagy can prime selfdestruction by cells, and some forms of selective autophagy and non-canonical forms of macroautophagy have been shown to be associated with cell demise. There is now mounting evidence that autophagy and apoptosis share several common regulatory elements that are crucial in any attempt to understand the dual role of autophagy in cell survival and cell death. The term 'autophagy' embraces several different mechanisms: microautophagy, macroautophagy and chaperone-mediated autophagy, 1 all of which are involved in the lysosomal degradation of cellular components. In this review, we will focus essentially on macroautophagy, because of the large body of data available about its cross talk with cell death. Macroautophagy (hereafter called 'autophagy') is a mechanism conserved among eukaryotic cells that starts with the formation of a multi-membrane-bound vacuole, known as an autophagosome, which ultimately fuses with the lysosomal compartment and the degradation of the sequestered material. 2 The seminal discovery of autophagy-related (ATG) genes initially in yeast and then in multicellular organisms 3,4 has led to an important breakthrough in the understanding of how autophagosomes are formed and of the part autophagy plays in cell physiology and human diseases. 1,5 To clarify how macroautophagy is modulated in response to stress situations, it is also absolutely essential to elucidate how the macroautophagy is regulated upstream of the Atg machinery. 6 Macroautophagy occurs at a basal rate in most cells, where it acts as a cytoplasmic quality-control mechanism to eliminate protein aggregates and damaged organelles. 1,5 The physiological importance of basal autophagy in maintaining tissue homeostasis has recently been demonstrated in conditional brain and liver Atg knockout mouse models. [7][8][9] These studies have demonstrated the role of autophagy in preventing the cytotoxic deposition of aggregate-prone proteins in the cytoplasm, and the contribution of autophagy to the elimination of ubiquitinated proteins that are efficient substrates for the proteasome.On the other hand, when the supply of nutrients is limited, starvation-induced autophagy contrib...

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Apoptosis induces expression of sphingosine kinase 1 to release sphingosine‐1‐phosphate as a “come‐and‐get‐me” signal

Cited by 316 publications

References 56 publications

Do not let death do us part: ‘find-me’ signals in communication between dying cells and the phagocytes

Do not let death do us part: ‘find-me’ signals in communication between dying cells and the phagocytes

Heme Oxygenase-1 Contributes to an Alternative Macrophage Activation Profile Induced by Apoptotic Cell Supernatants

Does autophagy have a license to kill mammalian cells?

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