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Clearance of apoptotic cells

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https://www.readbyqxmd.com/read/27919685/programmed-cell-clearance-from-nematodes-to-humans
#1
Katharina Klöditz, Yu-Zen Chen, Ding Xue, Bengt Fadeel
Programmed cell clearance is a highly regulated physiological process of elimination of dying cells that occurs rapidly and efficiently in healthy organisms. It thus ensures proper development as well as homeostasis. Recent studies have disclosed a considerable degree of conservation of cell clearance pathways between nematodes and higher organisms. The externalization of the anionic phospholipid phosphatidylserine (PS) has emerged as an important "eat-me" signal for phagocytes and its exposition on apoptotic cells is controlled by phospholipid translocases and scramblases...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27903567/increased-plasma-ige-accelerate-atherosclerosis-in-secreted-igm-deficiency
#2
Dimitrios Tsiantoulas, Ilze Bot, Maria Ozsvar Kozma, Laura Goederle, Thomas Perkmann, Karsten Hartvigsen, Daniel H Conrad, Johan Kuiper, Ziad Mallat, Christoph J Binder
RATIONALE: Deficiency of secreted IgM (sIgM(-/-)) accelerates atherosclerosis in Ldlr(-/-) mice. Several atheroprotective effects of increased levels of IgM antibodies have been suggested, including preventing inflammation induced by oxidized LDL and promoting apoptotic cell clearance. However, the mechanisms by which the lack of sIgM promotes lesion formation remain unknown. OBJECTIVE: To identify the mechanisms by which sIgM deficiency accelerates atherosclerosis in mice...
November 30, 2016: Circulation Research
https://www.readbyqxmd.com/read/27900389/the-clearance-of-cell-remnants-and-the-regeneration-of-the-injured-muscle-depend-on-soluble-pattern-recognition-receptor-ptx3
#3
Michela Vezzoli, Clara Sciorati, Lara Campana, Antonella Monno, Maria Giulia Doglio, Elena Rigamonti, Gianfranca Corna, Thierry Touvier, Alessandra Castiglioni, Annalisa Capobianco, Alberto Mantovani, Angelo A Manfredi, Cecilia Garlanda, Patrizia Rovere-Querini
OBJECTIVE: The signals causing the resolution of muscle inflammation are only partially characterized. The long pentraxin PTX3, which modulates leukocyte recruitment and activation, could contribute. METHODS: We analysed the expression of ptx3 after muscle injury and verified whether hematopoietic precursors are a source of the protein. The kinetics of regeneration and leukocytes infiltration, the accumulation of cell remnants and anti-histidyl-t-RNA synthetase autoantibodies were compared in wild-type and ptx3-deficient mice...
November 23, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27878656/mille-modis-morimur-we-die-in-a-thousand-ways
#4
Gaspar Banfalvi
Dying cells subjected to apoptotic programs are engulfed by neighboring cells or by professional phagocytes, without inflammation or immunological reactions in the tissue where apoptosis takes place. Apoptotic cells release danger-associated project signals to their neighbours, through different molecular patterns, stimulate antigen production and immune responses. Microenvironmental effects with several functional consequences indicate that cell death is a complex process and may take place in several ways...
November 23, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27872476/new-insights-into-the-immunopathogenesis-of-systemic-lupus-erythematosus
#5
REVIEW
George C Tsokos, Mindy S Lo, Patricia Costa Reis, Kathleen E Sullivan
The aetiology of systemic lupus erythematosus (SLE) is multifactorial, and includes contributions from the environment, stochastic factors, and genetic susceptibility. Great gains have been made in understanding SLE through the use of genetic variant identification, mouse models, gene expression studies, and epigenetic analyses. Collectively, these studies support the concept that defective clearance of immune complexes and biological waste (such as apoptotic cells), neutrophil extracellular traps, nucleic acid sensing, lymphocyte signalling, and interferon production pathways are all central to loss of tolerance and tissue damage...
November 22, 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27863012/maxed-out-macs-physiologic-cell-clearance-as-a-function-of-macrophage-phagocytic-capacity
#6
REVIEW
Clive S Zent, Michael R Elliott
The phagocytic clearance of host cells is important for eliminating dying cells and for the therapeutic clearance of antibody-targeted cells. As ubiquitous, motile and highly phagocytic immune cells, macrophages are principal players in the phagocytic removal of host cells throughout the body. In recent years great strides have been made in identifying the molecular mechanisms that control the recognition and phagocytosis of cells by macrophages. However, much less is known about the physical and metabolic constraints that govern the amount of cellular material macrophages can ingest and how these limitations affect the overall efficiency of host cell clearance in health and disease...
November 14, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27834816/targeting-the-tam-receptors-in-leukemia
#7
REVIEW
Madeline G Huey, Katherine A Minson, H Shelton Earp, Deborah DeRyckere, Douglas K Graham
Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma...
November 8, 2016: Cancers
https://www.readbyqxmd.com/read/27833165/genetic-and-pharmacological-inhibition-of-cdk9-drives-neutrophil-apoptosis-to-resolve-inflammation-in-zebrafish-in-vivo
#8
Laura J Hoodless, Christopher D Lucas, Rodger Duffin, Martin A Denvir, Christopher Haslett, Carl S Tucker, Adriano G Rossi
Neutrophilic inflammation is tightly regulated and subsequently resolves to limit tissue damage and promote repair. When the timely resolution of inflammation is dysregulated, tissue damage and disease results. One key control mechanism is neutrophil apoptosis, followed by apoptotic cell clearance by phagocytes such as macrophages. Cyclin-dependent kinase (CDK) inhibitor drugs induce neutrophil apoptosis in vitro and promote resolution of inflammation in rodent models. Here we present the first in vivo evidence, using pharmacological and genetic approaches, that CDK9 is involved in the resolution of neutrophil-dependent inflammation...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27828940/different-tissue-phagocytes-sample-apoptotic-cells-to-direct-distinct-homeostasis-programs
#9
Ryan J Cummings, Gaetan Barbet, Gerold Bongers, Boris M Hartmann, Kyle Gettler, Luciana Muniz, Glaucia C Furtado, Judy Cho, Sergio A Lira, J Magarian Blander
Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies. The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear...
November 9, 2016: Nature
https://www.readbyqxmd.com/read/27827458/microrna-126-overexpression-rescues-diabetes-induced-impairment-in-efferocytosis-of-apoptotic-cardiomyocytes
#10
Sahana Suresh Babu, Rajarajan A Thandavarayan, Darukeshwara Joladarashi, Prince Jeyabal, Shashirekha Krishnamurthy, Arvind Bhimaraj, Keith A Youker, Prasanna Krishnamurthy
Efferocytosis, a process of clearance of apoptotic cells by phagocytes, is essential for successful resolution of inflammation and maintenance of tissue homeostasis. Diabetes compromises the function of macrophages leading to adverse inflammatory response during wound healing, myocardial injury, atherosclerosis and autoimmune disorders. However, the effect of diabetes on macrophage-mediated efferocytosis of apoptotic cardiomyocytes (ACM) and the molecular mechanisms involved are not understood so far. In the present study we found that invitro efferocytosis of ACM was impaired in macrophages from db/db (diabetic) mice...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27821726/keratin-mediates-the-recognition-of-apoptotic-and-necrotic-cells-through-dendritic-cell-receptor-dec205-cd205
#11
Longxing Cao, Haishuang Chang, Xiangyi Shi, Chao Peng, Yongning He
Clearance of dead cells is critical for maintaining homeostasis and prevents autoimmunity and inflammation. When cells undergo apoptosis and necrosis, specific markers are exposed and recognized by the receptors on phagocytes. DEC205 (CD205) is an endocytotic receptor on dendritic cells with antigen presentation function and has been widely used in immune therapies for vaccine generation. It has been shown that human DEC205 recognizes apoptotic and necrotic cells in a pH-dependent fashion. However, the natural ligand(s) of DEC205 remains unknown...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27820945/macrophages-redirect-phagocytosis-by-non-professional-phagocytes-and-influence-inflammation
#12
Claudia Z Han, Ignacio J Juncadella, Jason M Kinchen, Monica W Buckley, Alexander L Klibanov, Kelly Dryden, Suna Onengut-Gumuscu, Uta Erdbrügger, Stephen D Turner, Yun M Shim, Kenneth S Tung, Kodi S Ravichandran
Professional phagocytes (such as macrophages) and non-professional phagocytes (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis. Although professional and non-professional macrophages reside in proximity in most tissues, whether they communicate with each other during cell clearance, and how this might affect inflammation, is not known. Here we show that macrophages, through the release of a soluble growth factor and microvesicles, alter the type of particles engulfed by non-professional phagocytes and influence their inflammatory response...
November 7, 2016: Nature
https://www.readbyqxmd.com/read/27814290/influence-of-nanoporous-poly-ether-imide-particle-extracts-on-human-aortic-endothelial-cells-haecs
#13
Reddi K Kumar, Sayantani Basu, Horst-Dieter Lemke, Joachim Jankowski, Karl Kratz, Andreas Lendlein, Sarada D Tetali
Accumulated uremic toxins like indoxyl sulphate, hippuric acid and p-cresyl sulphates in renal failure patients stimulate proinflammatory effects, and consequently kidney and cardiovascular diseases. Low clearance rate of these uremic toxins from the blood of uremic patients by convention techniques like hemodialysis is due to their strong covalent albumin binding (greater than 95%) and hydrophobic nature, which led to alternatives like usage of hydrophobic adsorber's in removing these toxins from the plasma of kidney patients...
November 4, 2016: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/27801848/the-gas6-tam-system-and-multiple-sclerosis
#14
REVIEW
Mattia Bellan, Mario Pirisi, Pier Paolo Sainaghi
Growth arrest specific 6 (Gas6) is a multimodular circulating protein, the biological actions of which are mediated by the interaction with three transmembrane tyrosine kinase receptors: Tyro3, Axl, and MerTK, collectively named TAM. Over the last few decades, many progresses have been done in the understanding of the biological activities of this highly pleiotropic system, which plays a role in the regulation of immune response, inflammation, coagulation, cell growth, and clearance of apoptotic bodies. Recent findings have further related Gas6 and TAM receptors to neuroinflammation in general and, specifically, to multiple sclerosis (MS)...
October 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27787652/transcriptional-control-of-apoptotic-cell-clearance-by-macrophage-nuclear-receptors
#15
Tamás Röszer
Apoptotic cell clearance by macrophages is key for normal tissue development and homeostasis. Nuclear receptors, such as peroxisome proliferator activated receptors (PPARs), liver X receptor (LXR), retinoic acid receptor (RAR), retinoid X receptor (RXR) and glucocorticoid receptor (GR) orchestrate this vital process. The underlying mechanism involves the transcriptional control of key genes of apoptotic cell recognition and internalization, such as Cd36, Mertk, Axl, C1qa, Tgm2, Abca1. In addition, apoptotic cell uptake leads to M2 activation of macrophages, and this process is also controlled at the gene transcription level by nuclear receptors...
October 27, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27782329/complement-in-removal-of-the-dead-balancing-inflammation
#16
REVIEW
Myriam Martin, Anna M Blom
Recognition and removal of apoptotic and necrotic cells must be efficient and highly controlled to avoid excessive inflammation and autoimmune responses to self. The complement system, a crucial part of innate immunity, plays an important role in this process. Thus, apoptotic and necrotic cells are recognized by complement initiators such as C1q, mannose binding lectin, ficolins, and properdin. This triggers complement activation and opsonization of cells with fragments of C3b, which enhances phagocytosis and thus ensures silent removal...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27775650/the-role-of-tam-family-receptors-in-immune-cell-function-implications-for-cancer-therapy
#17
Magdalena Paolino, Josef M Penninger
The TAM receptor protein tyrosine kinases-Tyro3, Axl, and Mer-are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases...
October 21, 2016: Cancers
https://www.readbyqxmd.com/read/27770461/depletion-of-myeloid-cells-exacerbates-hepatitis-and-induces-an-aberrant-increase-in-histone-h3-in-mouse-serum
#18
Xuehua Piao, Soh Yamazaki, Sachiko Komazawa-Sakon, Sanae Miyake, Osamu Nakabayashi, Takeyuki Kurosawa, Tetsuo Mikami, Minoru Tanaka, Nico Van Rooijen, Masaki Ohmuraya, Akira Oikawa, Yuko Kojima, Soichiro Kakuta, Yasuo Uchiyama, Masato Tanaka, Hiroyasu Nakano
: Tissue-resident macrophages and bone marrow (BM)-derived monocytes play a crucial role in the maintenance of tissue homeostasis; however, their contribution to recovery from acute tissue injury is not fully understood. To address this issue, we generated an acute murine liver injury model using hepatocyte-specific Cflar-deficient (Cflar(Hep-low) ) mice. Cellular FLICE-inhibitory protein (cFLIP) expression was downregulated in Cflar-deficient hepatocytes, which thereby increased susceptibility of hepatocytes to death receptor-induced apoptosis...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27743319/lipopolysaccharide-and-curcumin-co-stimulation-potentiates-olfactory-ensheathing-cell-phagocytosis-via-enhancing-their-activation
#19
Ding-Jun Hao, Cuicui Liu, Lingling Zhang, Bo Chen, Qian Zhang, Rui Zhang, Jing An, Jingjing Zhao, Mingmei Wu, Yi Wang, Alfred Simental, Baorong He, Hao Yang
The gradual deterioration following central nervous system (CNS) injuries or neurodegenerative disorders is usually accompanied by infiltration of degenerated and apoptotic neural tissue debris. A rapid and efficient clearance of these deteriorated cell products is of pivotal importance in creating a permissive environment for regeneration of those damaged neurons. Our recent report revealed that the phagocytic activity of olfactory ensheathing cells (OECs) can make a substantial contribution to neuronal growth in such a hostile environment...
October 14, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27723373/enhanced-autophagy-in-pulmonary-endothelial-cells-on-exposure-to-hiv-tat-and-morphine-role-in-hiv-related-pulmonary-arterial-hypertension
#20
Pranjali Dalvi, Himanshu Sharma, Mahendran Chinnappan, Miles Sanderson, Julie Allen, Ruoxi Zeng, Augustine Choi, Amy O'Brien-Ladner, Navneet K Dhillon
Intravenous drug use is one of the major risk factors for HIV-infection in HIV-related pulmonary arterial hypertension patients. We previously demonstrated exaggerated pulmonary vascular remodeling with enhanced apoptosis followed by increased proliferation of pulmonary endothelial cells on simultaneous exposure to both opioids and HIV protein(s). Here we hypothesize that the exacerbation of autophagy may be involved in the switching of endothelial cells from an early apoptotic state to later hyper-proliferative state...
October 10, 2016: Autophagy
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