The Experts below are selected from a list of 13488 Experts worldwide ranked by ideXlab platform
Christopher B Medina - One of the best experts on this subject based on the ideXlab platform.
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Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release
Nature, 2018Co-Authors: Sho Morioka, Justin S A Perry, Michael H Raymond, Christopher B Medina, Vlad Serbulea, Norbert Leitinger, Liyang Zhao, Yunlu Zhu, Suna Onengut-gumuscu, Sarah KucenasAbstract:Development and routine tissue homeostasis require a high turnover of apoptotic cells. These cells are removed by professional and non-professional Phagocytes via efferocytosis^ 1 . How a Phagocyte maintains its homeostasis while coordinating corpse uptake, processing ingested materials and secreting anti-inflammatory mediators is incompletely understood^ 1 , 2 . Here, using RNA sequencing to characterize the transcriptional program of Phagocytes actively engulfing apoptotic cells, we identify a genetic signature involving 33 members of the solute carrier (SLC) family of membrane transport proteins, in which expression is specifically modulated during efferocytosis, but not during antibody-mediated phagocytosis. We assessed the functional relevance of these SLCs in efferocytic Phagocytes and observed a robust induction of an aerobic glycolysis program, initiated by SLC2A1-mediated glucose uptake, with concurrent suppression of the oxidative phosphorylation program. The different steps of phagocytosis^ 2 —that is, ‘smell’ (‘find-me’ signals or sensing factors released by apoptotic cells), ‘taste’ (Phagocyte–apoptotic cell contact) and ‘ingestion’ (corpse internalization)—activated distinct and overlapping sets of genes, including several SLC genes, to promote glycolysis. SLC16A1 was upregulated after corpse uptake, increasing the release of lactate, a natural by-product of aerobic glycolysis^ 3 . Whereas glycolysis within Phagocytes contributed to actin polymerization and the continued uptake of corpses, lactate released via SLC16A1 promoted the establishment of an anti-inflammatory tissue environment. Collectively, these data reveal a SLC program that is activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake and show that glycolytic by-products of efferocytosis can influence surrounding cells. Distinct transcriptional programs are activated during different stages of apoptotic cell engulfment, including a unique program of genes coding for solute carrier proteins and enzymes in the glycolytic pathway.
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efferocytosis induces a novel slc program to promote glucose uptake and lactate release
Nature, 2018Co-Authors: Sho Morioka, Justin S A Perry, Michael H Raymond, Christopher B Medina, Suna Onengutgumuscu, Sarah Kucenas, Vlad Serbulea, Norbert Leitinger, Liyang Zhao, Jeffrey C RathmellAbstract:Development and routine tissue homeostasis require a high turnover of apoptotic cells. These cells are removed by professional and non-professional Phagocytes via efferocytosis1. How a Phagocyte maintains its homeostasis while coordinating corpse uptake, processing ingested materials and secreting anti-inflammatory mediators is incompletely understood1,2. Here, using RNA sequencing to characterize the transcriptional program of Phagocytes actively engulfing apoptotic cells, we identify a genetic signature involving 33 members of the solute carrier (SLC) family of membrane transport proteins, in which expression is specifically modulated during efferocytosis, but not during antibody-mediated phagocytosis. We assessed the functional relevance of these SLCs in efferocytic Phagocytes and observed a robust induction of an aerobic glycolysis program, initiated by SLC2A1-mediated glucose uptake, with concurrent suppression of the oxidative phosphorylation program. The different steps of phagocytosis2—that is, ‘smell’ (‘find-me’ signals or sensing factors released by apoptotic cells), ‘taste’ (Phagocyte–apoptotic cell contact) and ‘ingestion’ (corpse internalization)—activated distinct and overlapping sets of genes, including several SLC genes, to promote glycolysis. SLC16A1 was upregulated after corpse uptake, increasing the release of lactate, a natural by-product of aerobic glycolysis3. Whereas glycolysis within Phagocytes contributed to actin polymerization and the continued uptake of corpses, lactate released via SLC16A1 promoted the establishment of an anti-inflammatory tissue environment. Collectively, these data reveal a SLC program that is activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake and show that glycolytic by-products of efferocytosis can influence surrounding cells.
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do not let death do us part find me signals in communication between dying cells and the Phagocytes
Cell Death & Differentiation, 2016Co-Authors: Christopher B Medina, Kodi S RavichandranAbstract: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.
Sarah Kucenas - One of the best experts on this subject based on the ideXlab platform.
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Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release
Nature, 2018Co-Authors: Sho Morioka, Justin S A Perry, Michael H Raymond, Christopher B Medina, Vlad Serbulea, Norbert Leitinger, Liyang Zhao, Yunlu Zhu, Suna Onengut-gumuscu, Sarah KucenasAbstract:Development and routine tissue homeostasis require a high turnover of apoptotic cells. These cells are removed by professional and non-professional Phagocytes via efferocytosis^ 1 . How a Phagocyte maintains its homeostasis while coordinating corpse uptake, processing ingested materials and secreting anti-inflammatory mediators is incompletely understood^ 1 , 2 . Here, using RNA sequencing to characterize the transcriptional program of Phagocytes actively engulfing apoptotic cells, we identify a genetic signature involving 33 members of the solute carrier (SLC) family of membrane transport proteins, in which expression is specifically modulated during efferocytosis, but not during antibody-mediated phagocytosis. We assessed the functional relevance of these SLCs in efferocytic Phagocytes and observed a robust induction of an aerobic glycolysis program, initiated by SLC2A1-mediated glucose uptake, with concurrent suppression of the oxidative phosphorylation program. The different steps of phagocytosis^ 2 —that is, ‘smell’ (‘find-me’ signals or sensing factors released by apoptotic cells), ‘taste’ (Phagocyte–apoptotic cell contact) and ‘ingestion’ (corpse internalization)—activated distinct and overlapping sets of genes, including several SLC genes, to promote glycolysis. SLC16A1 was upregulated after corpse uptake, increasing the release of lactate, a natural by-product of aerobic glycolysis^ 3 . Whereas glycolysis within Phagocytes contributed to actin polymerization and the continued uptake of corpses, lactate released via SLC16A1 promoted the establishment of an anti-inflammatory tissue environment. Collectively, these data reveal a SLC program that is activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake and show that glycolytic by-products of efferocytosis can influence surrounding cells. Distinct transcriptional programs are activated during different stages of apoptotic cell engulfment, including a unique program of genes coding for solute carrier proteins and enzymes in the glycolytic pathway.
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efferocytosis induces a novel slc program to promote glucose uptake and lactate release
Nature, 2018Co-Authors: Sho Morioka, Justin S A Perry, Michael H Raymond, Christopher B Medina, Suna Onengutgumuscu, Sarah Kucenas, Vlad Serbulea, Norbert Leitinger, Liyang Zhao, Jeffrey C RathmellAbstract:Development and routine tissue homeostasis require a high turnover of apoptotic cells. These cells are removed by professional and non-professional Phagocytes via efferocytosis1. How a Phagocyte maintains its homeostasis while coordinating corpse uptake, processing ingested materials and secreting anti-inflammatory mediators is incompletely understood1,2. Here, using RNA sequencing to characterize the transcriptional program of Phagocytes actively engulfing apoptotic cells, we identify a genetic signature involving 33 members of the solute carrier (SLC) family of membrane transport proteins, in which expression is specifically modulated during efferocytosis, but not during antibody-mediated phagocytosis. We assessed the functional relevance of these SLCs in efferocytic Phagocytes and observed a robust induction of an aerobic glycolysis program, initiated by SLC2A1-mediated glucose uptake, with concurrent suppression of the oxidative phosphorylation program. The different steps of phagocytosis2—that is, ‘smell’ (‘find-me’ signals or sensing factors released by apoptotic cells), ‘taste’ (Phagocyte–apoptotic cell contact) and ‘ingestion’ (corpse internalization)—activated distinct and overlapping sets of genes, including several SLC genes, to promote glycolysis. SLC16A1 was upregulated after corpse uptake, increasing the release of lactate, a natural by-product of aerobic glycolysis3. Whereas glycolysis within Phagocytes contributed to actin polymerization and the continued uptake of corpses, lactate released via SLC16A1 promoted the establishment of an anti-inflammatory tissue environment. Collectively, these data reveal a SLC program that is activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake and show that glycolytic by-products of efferocytosis can influence surrounding cells.
Sho Morioka - One of the best experts on this subject based on the ideXlab platform.
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Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release
Nature, 2018Co-Authors: Sho Morioka, Justin S A Perry, Michael H Raymond, Christopher B Medina, Vlad Serbulea, Norbert Leitinger, Liyang Zhao, Yunlu Zhu, Suna Onengut-gumuscu, Sarah KucenasAbstract:Development and routine tissue homeostasis require a high turnover of apoptotic cells. These cells are removed by professional and non-professional Phagocytes via efferocytosis^ 1 . How a Phagocyte maintains its homeostasis while coordinating corpse uptake, processing ingested materials and secreting anti-inflammatory mediators is incompletely understood^ 1 , 2 . Here, using RNA sequencing to characterize the transcriptional program of Phagocytes actively engulfing apoptotic cells, we identify a genetic signature involving 33 members of the solute carrier (SLC) family of membrane transport proteins, in which expression is specifically modulated during efferocytosis, but not during antibody-mediated phagocytosis. We assessed the functional relevance of these SLCs in efferocytic Phagocytes and observed a robust induction of an aerobic glycolysis program, initiated by SLC2A1-mediated glucose uptake, with concurrent suppression of the oxidative phosphorylation program. The different steps of phagocytosis^ 2 —that is, ‘smell’ (‘find-me’ signals or sensing factors released by apoptotic cells), ‘taste’ (Phagocyte–apoptotic cell contact) and ‘ingestion’ (corpse internalization)—activated distinct and overlapping sets of genes, including several SLC genes, to promote glycolysis. SLC16A1 was upregulated after corpse uptake, increasing the release of lactate, a natural by-product of aerobic glycolysis^ 3 . Whereas glycolysis within Phagocytes contributed to actin polymerization and the continued uptake of corpses, lactate released via SLC16A1 promoted the establishment of an anti-inflammatory tissue environment. Collectively, these data reveal a SLC program that is activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake and show that glycolytic by-products of efferocytosis can influence surrounding cells. Distinct transcriptional programs are activated during different stages of apoptotic cell engulfment, including a unique program of genes coding for solute carrier proteins and enzymes in the glycolytic pathway.
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efferocytosis induces a novel slc program to promote glucose uptake and lactate release
Nature, 2018Co-Authors: Sho Morioka, Justin S A Perry, Michael H Raymond, Christopher B Medina, Suna Onengutgumuscu, Sarah Kucenas, Vlad Serbulea, Norbert Leitinger, Liyang Zhao, Jeffrey C RathmellAbstract:Development and routine tissue homeostasis require a high turnover of apoptotic cells. These cells are removed by professional and non-professional Phagocytes via efferocytosis1. How a Phagocyte maintains its homeostasis while coordinating corpse uptake, processing ingested materials and secreting anti-inflammatory mediators is incompletely understood1,2. Here, using RNA sequencing to characterize the transcriptional program of Phagocytes actively engulfing apoptotic cells, we identify a genetic signature involving 33 members of the solute carrier (SLC) family of membrane transport proteins, in which expression is specifically modulated during efferocytosis, but not during antibody-mediated phagocytosis. We assessed the functional relevance of these SLCs in efferocytic Phagocytes and observed a robust induction of an aerobic glycolysis program, initiated by SLC2A1-mediated glucose uptake, with concurrent suppression of the oxidative phosphorylation program. The different steps of phagocytosis2—that is, ‘smell’ (‘find-me’ signals or sensing factors released by apoptotic cells), ‘taste’ (Phagocyte–apoptotic cell contact) and ‘ingestion’ (corpse internalization)—activated distinct and overlapping sets of genes, including several SLC genes, to promote glycolysis. SLC16A1 was upregulated after corpse uptake, increasing the release of lactate, a natural by-product of aerobic glycolysis3. Whereas glycolysis within Phagocytes contributed to actin polymerization and the continued uptake of corpses, lactate released via SLC16A1 promoted the establishment of an anti-inflammatory tissue environment. Collectively, these data reveal a SLC program that is activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake and show that glycolytic by-products of efferocytosis can influence surrounding cells.
John W. Eaton - One of the best experts on this subject based on the ideXlab platform.
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mast cells mediate acute inflammatory responses to implanted biomaterials
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Liping Tang, Timothy A Jennings, John W. EatonAbstract:Implanted biomaterials trigger acute and chronic inflammatory responses. The mechanisms involved in such acute inflammatory responses can be arbitrarily divided into Phagocyte transmigration, chemotaxis, and adhesion to implant surfaces. We earlier observed that two chemokines-macrophage inflammatory protein 1alpha/monocyte chemoattractant protein 1-and the Phagocyte integrin Mac-1 (CD11b/CD18)/surface fibrinogen interaction are, respectively, required for Phagocyte chemotaxis and adherence to biomaterial surfaces. However, it is still not clear how the initial transmigration of Phagocytes through the endothelial barrier into the area of the implant is triggered. Because implanted biomaterials elicit histaminic responses in the surrounding tissue, and histamine release is known to promote rapid diapedesis of inflammatory cells, we evaluated the possible role of histamine and mast cells in the recruitment of Phagocytes to biomaterial implants. Using i.p. and s. c. implantation of polyethylene terephthalate disks in mice we find: (i) Extensive degranulation of mast cells, accompanied by histamine release, occurs adjacent to short-term i.p. implants. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists (pyrilamine and famotidine, respectively) greatly diminishes recruitment and adhesion of both neutrophils (<20% of control) and monocytes/macrophages (<30% of control) to implants. (iii) Congenitally mast cell-deficient mice also exhibit markedly reduced accumulation of Phagocytes on both i.p. and s.c implants. (iv) Finally, mast cell reconstitution of mast cell-deficient mice restores "normal" inflammatory responses to biomaterial implants. We conclude that mast cells and their granular products, especially histamine, are important in recruitment of inflammatory cells to biomaterial implants. Improved knowledge of such responses may permit purposeful modulation of both acute and chronic inflammation affecting implanted biomaterials.
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mast cells mediate acute inflammatory responses to implanted biomaterials histamineyPhagocytes
1998Co-Authors: Liping Tang, Imothy T A Jennings, John W. EatonAbstract:Implanted biomaterials trigger acute and chronic inf lammatory responses. The mechanisms involved in such acute inf lammatory responses can be arbitrarily divided into Phagocyte transmigration, chemotaxis, and adhesion to implant surfaces. We earlier observed that two chemokines— macrophage inf lammatory protein 1aymonocyte chemoat- tractant protein 1—and the Phagocyte integrin Mac-1 (CD11byCD18)ysurface fibrinogen interaction are, respec- tively, required for Phagocyte chemotaxis and adherence to biomaterial surfaces. However, it is still not clear how the initial transmigration of Phagocytes through the endothelial barrier into the area of the implant is triggered. Because implanted biomaterials elicit histaminic responses in the surrounding tissue, and histamine release is known to pro- mote rapid diapedesis of inf lammatory cells, we evaluated the possible role of histamine and mast cells in the recruitment of Phagocytes to biomaterial implants. Using i.p. and s.c. im- plantation of polyethylene terephthalate disks in mice we find: (i) Extensive degranulation of mast cells, accompanied by histamine release, occurs adjacent to short-term i.p. implants. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists (pyrilamine and famotidine, respec- tively) greatly diminishes recruitment and adhesion of both neutrophils (<20% of control) and monocytesymacrophages (<30% of control) to implants. (iii) Congenitally mast cell- deficient mice also exhibit markedly reduced accumulation of Phagocytes on both i.p. and s.c implants. (iv) Finally, mast cell reconstitution of mast cell-deficient mice restores ''normal'' inf lammatory responses to biomaterial implants. We con- clude that mast cells and their granular products, especially histamine, are important in recruitment of inf lammatory cells to biomaterial implants. Improved knowledge of such re- sponses may permit purposeful modulation of both acute and chronic inf lammation affecting implanted biomaterials.
Jeffrey C Rathmell - One of the best experts on this subject based on the ideXlab platform.
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efferocytosis induces a novel slc program to promote glucose uptake and lactate release
Nature, 2018Co-Authors: Sho Morioka, Justin S A Perry, Michael H Raymond, Christopher B Medina, Suna Onengutgumuscu, Sarah Kucenas, Vlad Serbulea, Norbert Leitinger, Liyang Zhao, Jeffrey C RathmellAbstract:Development and routine tissue homeostasis require a high turnover of apoptotic cells. These cells are removed by professional and non-professional Phagocytes via efferocytosis1. How a Phagocyte maintains its homeostasis while coordinating corpse uptake, processing ingested materials and secreting anti-inflammatory mediators is incompletely understood1,2. Here, using RNA sequencing to characterize the transcriptional program of Phagocytes actively engulfing apoptotic cells, we identify a genetic signature involving 33 members of the solute carrier (SLC) family of membrane transport proteins, in which expression is specifically modulated during efferocytosis, but not during antibody-mediated phagocytosis. We assessed the functional relevance of these SLCs in efferocytic Phagocytes and observed a robust induction of an aerobic glycolysis program, initiated by SLC2A1-mediated glucose uptake, with concurrent suppression of the oxidative phosphorylation program. The different steps of phagocytosis2—that is, ‘smell’ (‘find-me’ signals or sensing factors released by apoptotic cells), ‘taste’ (Phagocyte–apoptotic cell contact) and ‘ingestion’ (corpse internalization)—activated distinct and overlapping sets of genes, including several SLC genes, to promote glycolysis. SLC16A1 was upregulated after corpse uptake, increasing the release of lactate, a natural by-product of aerobic glycolysis3. Whereas glycolysis within Phagocytes contributed to actin polymerization and the continued uptake of corpses, lactate released via SLC16A1 promoted the establishment of an anti-inflammatory tissue environment. Collectively, these data reveal a SLC program that is activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake and show that glycolytic by-products of efferocytosis can influence surrounding cells.
