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Efferocytosis

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https://www.readbyqxmd.com/read/29118755/apoptotic-cells-induced-signaling-for-immune-homeostasis-in-macrophages-and-dendritic-cells
#1
REVIEW
Uriel Trahtemberg, Dror Mevorach
Inefficient and abnormal clearance of apoptotic cells (efferocytosis) contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs), and contributes to maintenance of peripheral tolerance. As many as 3 × 10(8) cells undergo apoptosis every hour in our bodies, and one of the primary "eat me" signals expressed by apoptotic cells is phosphatidylserine (PtdSer)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29070674/orchestrating-role-of-apoptosis-inhibitor-of-macrophage-in-the-resolution-of-acute-lung-injury
#2
Hiroki Kimura, Masaru Suzuki, Satoshi Konno, Hideo Shindou, Takao Shimizu, Takahide Nagase, Toru Miyazaki, Masaharu Nishimura
Appropriate resolution of inflammation is known to be essential in tissue homeostasis. In this study, we evaluated the significance of a macrophage-derived soluble protein, apoptosis inhibitor of macrophage (AIM), in LPS-induced lung injury in mice. After oropharyngeal administration of LPS, the level of free-form serum AIM increased on days 2-4, accompanied by the resolution of inflammation, which was observed in the cellular profile of bronchoalveolar lavage fluid. In an experiment using wild-type (WT) and AIM(-/-) mice, the resolution of inflammation was accelerated in AIM(-/-) mice when compared with the WT mice, which was reversed when recombinant AIM protein was administered...
October 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29053156/atherosclerosis-mitochondrial-fission-is-crucial-for-efferocytosis
#3
Irene Fernanández-Ruiz
No abstract text is available yet for this article.
December 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29053142/resolution-of-inflammation-and-sepsis-survival-are-improved-by-dietary-%C3%AE-3-fatty-acids
#4
Andreas Körner, Martin Schlegel, Julia Theurer, Hannes Frohnmeyer, Michael Adolph, Marieke Heijink, Martin Giera, Peter Rosenberger, Valbona Mirakaj
Critical conditions such as sepsis following infection or traumatic injury disturb the complex state of homeostasis that may lead to uncontrolled inflammation resulting in organ failure, shock and death. They are associated with endogenous mediators that control the onset of acute inflammatory response, but the central problem remains the complete resolution of inflammation. Omega-3 enriched lipid emulsions (Ω-3(+) LEs) were used in experimental studies and clinical trials to establish homeostasis, yet with little understanding about their role on the resolution of inflammation and tissue regeneration...
October 20, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29030012/mafb-enhances-efferocytosis-in-raw264-7-macrophages-by-regulating-axl-expression
#5
Masamichi Sato, Yoko Shibata, Sumito Inoue, Akira Igarashi, Yoshikane Tokairin, Keiko Yamauchi, Tomomi Kimura, Takako Nemoto, Kento Sato, Hiroshi Nakano, Shuichi Abe, Michiko Nishiwaki, Maki Kobayashi, Sujeong Yang, Yukihiro Minegishi, Kodai Furuyama, Isao Kubota
The transcription factor MafB is involved in cellular differentiation and phagocytosis in macrophages. Macrophages phagocytose apoptotic cells in vivo; this process, which is known as efferocytosis, requires Axl receptor tyrosine kinase (Axl) activity. However, the association between MafB and efferocytosis, as well as that between MafB and Axl, in macrophages is unknown. We hypothesized that MafB modulates macrophage efferocytosis by regulating Axl expression. Fluorescent-labeled apoptotic thymocytes were added to RAW264...
October 6, 2017: Immunobiology
https://www.readbyqxmd.com/read/29027226/efferocytosis-of-dying-cells-differentially-modulate-immunological-outcomes-in-tumor-microenvironment
#6
REVIEW
Sushil Kumar, David Calianese, Raymond B Birge
Programmed cell death (apoptosis) is an integral part of tissue homeostasis in complex organisms, allowing for tissue turnover, repair, and renewal while simultaneously inhibiting the release of self antigens and danger signals from apoptotic cell-derived constituents that can result in immune activation, inflammation, and autoimmunity. Unlike cells in culture, the physiological fate of cells that die by apoptosis in vivo is their rapid recognition and engulfment by phagocytic cells (a process called efferocytosis)...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29024644/m-%C3%A2-tuberculosis-induced-necrosis-of-infected-neutrophils-promotes-bacterial-growth-following-phagocytosis-by-macrophages
#7
Tobias Dallenga, Urska Repnik, Björn Corleis, Jacqueline Eich, Rudolph Reimer, Gareth W Griffiths, Ulrich E Schaible
Neutrophils represent the main infected cell population in the lungs of active tuberculosis patients. Efficient removal of infected and dying neutrophils is required to protect the surrounding tissue from bioactive neutrophil molecules and subsequent pathological sequelae. While the removal of apoptotic M. tuberculosis (Mtb)-infected cells, or efferocytosis, is considered beneficial for host defense, little is known about Mtb-infected necrotic neutrophils. We found that Mtb induces necrosis of human neutrophils in an ESX-1-dependent manner, and neutrophil-produced reactive oxygen species (ROS) drive this necrosis...
October 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28972541/camkii%C3%AE-suppresses-an-efferocytosis-pathway-in-macrophages-and-promotes-atherosclerotic-plaque-necrosis
#8
Amanda C Doran, Lale Ozcan, Bishuang Cai, Ze Zheng, Gabrielle Fredman, Christina C Rymond, Bernhard Dorweiler, Judith C Sluimer, Joanne Hsieh, George Kuriakose, Alan R Tall, Ira Tabas
Atherosclerosis is the underlying etiology of cardiovascular disease, the leading cause of death worldwide. Atherosclerosis is a heterogeneous disease in which only a small fraction of lesions lead to heart attack, stroke, or sudden cardiac death. A distinct type of plaque containing large necrotic cores with thin fibrous caps often precipitates these acute events. Here, we show that Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ) in macrophages plays a major role in the development of necrotic, thin-capped plaques...
November 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28942921/mitochondrial-fission-promotes-the-continued-clearance-of-apoptotic-cells-by-macrophages
#9
Ying Wang, Manikandan Subramanian, Arif Yurdagul, Valéria C Barbosa-Lorenzi, Bishuang Cai, Jaime de Juan-Sanz, Timothy A Ryan, Masatoshi Nomura, Frederick R Maxfield, Ira Tabas
Clearance of apoptotic cells (ACs) by phagocytes (efferocytosis) prevents post-apoptotic necrosis and dampens inflammation. Defective efferocytosis drives important diseases, including atherosclerosis. For efficient efferocytosis, phagocytes must be able to internalize multiple ACs. We show here that uptake of multiple ACs by macrophages requires dynamin-related protein 1 (Drp1)-mediated mitochondrial fission, which is triggered by AC uptake. When mitochondrial fission is disabled, AC-induced increase in cytosolic calcium is blunted owing to mitochondrial calcium sequestration, and calcium-dependent phagosome formation around secondarily encountered ACs is impaired...
October 5, 2017: Cell
https://www.readbyqxmd.com/read/28801233/t-cell-zone-resident-macrophages-silently-dispose-of-apoptotic-cells-in-the-lymph-node
#10
Myriam Baratin, Léa Simon, Audrey Jorquera, Clément Ghigo, Doulaye Dembele, Jonathan Nowak, Rebecca Gentek, Stephan Wienert, Frederick Klauschen, Bernard Malissen, Marc Dalod, Marc Bajénoff
In lymph nodes (LNs), dendritic cells (DCs) are thought to dispose of apoptotic cells, a function pertaining to macrophages in other tissues. We found that a population of CX3CR1(+) MERTK(+) cells located in the T cell zone of LNs, previously identified as DCs, are efferocytic macrophages. Lineage-tracing experiments and shield chimeras indicated that these T zone macrophages (TZM) are long-lived macrophages seeded in utero and slowly replaced by blood monocytes after birth. Imaging the LNs of mice in which TZM and DCs express different fluorescent proteins revealed that TZM-and not DCs-act as the only professional scavengers, clearing apoptotic cells in the LN T cell zone in a CX3CR1-dependent manner...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28768810/mouse-macrophages-show-different-requirements-for-phosphatidylserine-receptor-tim4-in-efferocytosis
#11
Yuichi Yanagihashi, Katsumori Segawa, Ryota Maeda, Yo-Ichi Nabeshima, Shigekazu Nagata
Protein S (ProS) and growth arrest-specific 6 (Gas6) bind to phosphatidylserine (PtdSer) and induce efferocytosis upon binding TAM-family receptors (Tyro3, Axl, and Mer). Here, we produced mouse ProS, Gas6, and TAM-receptor extracellular region fused to IgG fragment crystallizable region in HEK293T cells. ProS and Gas6 bound Ca(2+) dependently to PtdSer (Kd 20-40 nM), Mer, and Tyro3 (Kd 15-50 nM). Gas6 bound Axl strongly (Kd < 1.0 nM), but ProS did not bind Axl. Using NIH 3T3-based cell lines expressing a single TAM receptor, we showed that TAM-mediated efferocytosis was determined by the receptor-binding ability of ProS and Gas6...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28734635/programmed-cell-death-and-inflammation-winter-is-coming
#12
REVIEW
Joseph P Kolb, Thomas H Oguin, Andrew Oberst, Jennifer Martinez
The life of an organism requires the assistance of an unlikely process: programmed cell death. Both development and the maintenance of homeostasis result in the production of superfluous cells that must eventually be disposed of. Furthermore, programmed cell death can also represent a defense mechanism; for example, by depriving pathogens of a replication niche. The responsibility of handling these dead cells falls on phagocytes of the immune system, which surveil their surroundings for dying or dead cells and efficiently clear them in a quiescent manner...
October 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28720835/exophagy-of-annexin-a2-via-rab11-rab8a-and-rab27a-in-ifn-%C3%AE-stimulated-lung-epithelial-cells
#13
Ying-Da Chen, Yi-Ting Fang, Yi-Lin Cheng, Chiou-Feng Lin, Li-Jin Hsu, Shu-Ying Wang, Robert Anderson, Chih-Peng Chang, Yee-Shin Lin
Annexin A2 (ANXA2), a phospholipid-binding protein, has multiple biological functions depending on its cellular localization. We previously demonstrated that IFN-γ-triggered ANXA2 secretion is associated with exosomal release. Here, we show that IFN-γ-induced autophagy is essential for the extracellular secretion of ANXA2 in lung epithelial cells. We observed colocalization of ANXA2-containing autophagosomes with multivesicular bodies (MVBs) after IFN-γ stimulation, followed by exosomal release. IFN-γ-induced exophagic release of ANXA2 could not be observed in ATG5-silenced or mutant RAB11-expressing cells...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698173/interferon-regulatory-factor-5-controls-necrotic-core-formation-in-atherosclerotic-lesions-by-impairing-efferocytosis
#14
Anusha N Seneviratne, Andreas Edsfeldt, Jennifer E Cole, Christina Kassiteridi, Maarten Swart, Inhye Park, Patricia Green, Tariq Khoyratty, David Saliba, Michael E Goddard, Stephen N Sansom, Isabel Goncalves, Rob Krams, Irina A Udalova, Claudia Monaco
BACKGROUND: Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis) promotes lesion growth and establishment of a necrotic core. The transcription factor interferon regulatory factor (IRF)-5 is an important modulator of myeloid function and programming. We sought to investigate whether IRF5 affects the formation and phenotype of atherosclerotic lesions. METHODS: We investigated the role of IRF5 in atherosclerosis in 2 complementary models...
September 19, 2017: Circulation
https://www.readbyqxmd.com/read/28686604/boosting-efferocytosis-in-alveolar-space-using-bcg-vaccine-to-protect-host-against-influenza-pneumonia
#15
Sanjay Mukherjee, Renuka Subramaniam, Han Chen, Anthony Smith, Shiva Keshava, Homayoun Shams
Efferocytosis by alveolar phagocytes (APs) is pivotal in maintenance of lung homeostasis. Increased efferocytosis by APs results in protection against lethal acute lung injury due to pulmonary infections whereas defective efferocytosis by APs results in chronic lung inflammation. In this report, we show that pulmonary delivery of Bacillus Calmette-Guerin (BCG) significantly enhances efferocytosis by APs. Increased efferocytosis by APs maintains lung homeostasis and protects mice against lethal influenza pneumonia...
2017: PloS One
https://www.readbyqxmd.com/read/28671983/isoflurane-promotes-phagocytosis-of-apoptotic-neutrophils-through-ampk-mediated-adam17-mer-signaling
#16
Xueke Du, Chunling Jiang, Yang Lv, Randal O Dull, You-Yang Zhao, David E Schwartz, Guochang Hu
A patient's recovery from lung inflammatory injury or development of multi-system organ failure is determined by the host's ability to resolve inflammation and repair tissue damage, both of which require the clearance of apoptotic neutrophils by macrophages (efferocytosis). Here, we investigated the effects of isoflurane on macrophage efferocytosis and resolution of lung inflammatory injury. Treatment of murine bone marrow-derived macrophages (BMDMs) or alveolar macrophages with isoflurane dramatically enhanced phagocytosis of apoptotic neutrophils...
2017: PloS One
https://www.readbyqxmd.com/read/28613937/cell-removal-efferocytosis
#17
Peter M Henson
In metazoans, removal of cells in situ is involved in larval maturation, metamorphosis, and embryonic development. In adults, such cell removal plays a role in the homeostatic maintenance of cell numbers and tissue integrity as well as in the response to cell injury and damage. This removal involves uptake of the whole or fragmented target cells into phagocytes. Depending on the organism, these latter may be near-neighbor tissue cells and/or professional phagocytes such as, in vertebrates, members of the myeloid family of cells, especially macrophages...
October 6, 2017: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/28605477/mertk-as-a-therapeutic-target-in-glioblastoma
#18
Jing Wu, Lauren N Frady, Ryan E Bash, Stephanie M Cohen, Allison N Schorzman, Yu-Ting Su, David M Irvin, William C Zamboni, Xiaodong Wang, Stephen V Frye, Matthew G Ewend, Erik P Sulman, Mark R Gilbert, H Shelton Earp, C Ryan Miller
Background: Glioma-associated macrophages and microglia (GAMs) are components of the glioblastoma (GBM) microenvironment that express MerTK, a receptor tyrosine kinase that triggers efferocytosis and can suppress innate immune responses. The aim of the study was to define MerTK as a therapeutic target using an orally bioavailable inhibitor, UNC2025. Methods: We examined MerTK expression in tumor cells and macrophages in matched patient GBM samples by double-label immunohistochemistry...
June 12, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28600866/bone-mass-is-compromised-by-the-chemotherapeutic-trabectedin-in-association-with-effects-on-osteoblasts-and-macrophage-efferocytosis
#19
Benjamin P Sinder, Laura Zweifler, Amy J Koh, Megan N Michalski, Lorenz C Hofbauer, Jose Ignacio Aguirre, Hernan Roca, Laurie K McCauley
Macrophages have established roles supporting bone formation. Despite their professional phagocytic nature, the role of macrophage phagocytosis in bone homeostasis is not well understood. Interestingly, apoptosis is a pivotal feature of cellular regulation and the primary fate of osteoblasts is apoptosis. Efferocytosis (phagocytosis of apoptotic cells) is a key physiologic process for the homeostasis of many tissues, and is associated with expression of osteoinductive factors. To test effects of macrophage depletion and compromised phagocytosis on bone, 16-week-old male C57BL/6J mice were treated with trabectedin-a chemotherapeutic with established anti-macrophage effects...
October 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28594406/simvastatin-treatment-boosts-benefits-of-apoptotic-cell-infusion-in-murine-lung-fibrosis
#20
Ye-Ji Lee, Meung-Joo Kim, Young-So Yoon, Youn-Hee Choi, Hee-Sun Kim, Jihee Lee Kang
A single early-phase infusion of apoptotic cells can inhibit bleomycin-induced lung inflammation and fibrosis; however, it is unknown whether these effects can be enhanced with additional infusions and/or statin treatment. Here, we investigated whether an increased frequency of apoptotic cell injection, with or without efferocytosis enhancer simvastatin, facilitates therapeutic efficacy. An additional injection of apoptotic cells during the intermediate phase (7 days post-bleomycin treatment) or simvastatin administration alone on days 7-13 post-treatment did not promote anti-fibrotic responses beyond those induced by a single early apoptotic cell infusion alone...
June 8, 2017: Cell Death & Disease
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