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Clearance of apoptotic cells

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https://www.readbyqxmd.com/read/28432377/emerging-roles-of-calpain-proteolytic-systems-in-macrophage-cholesterol-handling
#1
REVIEW
Takuro Miyazaki, Akira Miyazaki
Calpains are Ca(2+)-dependent intracellular proteases that play central roles in the post-translational processing of functional proteins. In mammals, calpain proteolytic systems comprise the endogenous inhibitor calpastatin as well as 15 homologues of the catalytic subunits and two homologues of the regulatory subunits. Recent pharmacological and gene targeting studies in experimental animal models have revealed the contribution of conventional calpains, which consist of the calpain-1 and -2 isozymes, to atherosclerotic diseases...
April 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28428217/microrna-33-regulates-macrophage-autophagy-in-atherosclerosis
#2
Mireille Ouimet, Hasini Ediriweera, Milessa Silva Afonso, Bhama Ramkhelawon, Ragunath Singaravelu, Xianghai Liao, Rachel C Bandler, Karishma Rahman, Edward A Fisher, Katey J Rayner, John P Pezacki, Ira Tabas, Kathryn J Moore
OBJECTIVE: Defective autophagy in macrophages leads to pathological processes that contribute to atherosclerosis, including impaired cholesterol metabolism and defective efferocytosis. Autophagy promotes the degradation of cytoplasmic components in lysosomes and plays a key role in the catabolism of stored lipids to maintain cellular homeostasis. microRNA-33 (miR-33) is a post-transcriptional regulator of genes involved in cholesterol homeostasis, yet the complete mechanisms by which miR-33 controls lipid metabolism are unknown...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28424218/gop-1-promotes-apoptotic-cell-degradation-by-activating-the-small-gtpase-rab2-in-c-elegans
#3
Jianhua Yin, Yaling Huang, Pengfei Guo, Siqi Hu, Sawako Yoshina, Nan Xuan, Qiwen Gan, Shohei Mitani, Chonglin Yang, Xiaochen Wang
Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within plasma membrane-derived phagosomes. Maturation of phagosomes involves a series of membrane-remodeling events that are governed by the sequential actions of Rab GTPases and lead to formation of phagolysosomes, where cell corpses are degraded. Here we identified gop-1 as a novel regulator of apoptotic cell clearance in Caenorhabditis elegans Loss of gop-1 affects phagosome maturation through the RAB-5-positive stage, causing defects in phagosome acidification and phagolysosome formation, phenotypes identical to and unaffected by loss of unc-108, the C...
April 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28419128/cytoskeletal-stability-and-metabolic-alterations-in-primary-human-macrophages-in-long-term-microgravity
#4
Svantje Tauber, Beatrice A Lauber, Katrin Paulsen, Liliana E Layer, Martin Lehmann, Swantje Hauschild, Naomi R Shepherd, Jennifer Polzer, Jürgen Segerer, Cora S Thiel, Oliver Ullrich
The immune system is one of the most affected systems of the human body during space flight. The cells of the immune system are exceptionally sensitive to microgravity. Thus, serious concerns arise, whether space flight associated weakening of the immune system ultimately precludes the expansion of human presence beyond the Earth's orbit. For human space flight, it is an urgent need to understand the cellular and molecular mechanisms by which altered gravity influences and changes the functions of immune cells...
2017: PloS One
https://www.readbyqxmd.com/read/28414292/dendritic-cells-expressing-immunoreceptor-cd300f-are-critical-for-controlling-chronic-gut-inflammation
#5
Ha-Na Lee, Linjie Tian, Nicolas Bouladoux, Jacquice Davis, Mariam Quinones, Yasmine Belkaid, John E Coligan, Konrad Krzewski
Proinflammatory cytokine overproduction and excessive cell death, coupled with impaired clearance of apoptotic cells, have been implicated as causes of failure to resolve gut inflammation in inflammatory bowel diseases. Here we have found that dendritic cells expressing the apoptotic cell-recognizing receptor CD300f play a crucial role in regulating gut inflammatory responses in a murine model of colonic inflammation. CD300f-deficient mice failed to resolve dextran sulfate sodium-induced colonic inflammation as a result of defects in dendritic cell function that were associated with abnormal accumulation of apoptotic cells in the gut...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28412392/diminished-airway-macrophage-expression-of-the-axl-receptor-tyrosine-kinase-is-associated-with-defective-efferocytosis-in-asthma
#6
Aleksander M Grabiec, Nicholas Denny, John A Doherty, Kaisa E Happonen, Jenny Hankinson, Emma Connolly, Mark E Fife, Toshifumi Fujimori, Naoya Fujino, Anu Goenka, Susan Holden, Gaël Tavernier, Rajesh Shah, Peter C Cook, Andrew S MacDonald, Robert M Niven, Björn Dahlbäck, Stephen J Fowler, Angela Simpson, Tracy Hussell
The apoptotic cell recognition receptor Axl is highly expressed on human airway/alveolar macrophages, its expression is driven by the lung microenvironment and is significantly reduced in asthma, which may explain defects in apoptotic cell clearance.
April 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28409016/surface-complement-c3-fragments-and-cellular-binding-of-microparticles-in-patients-with-sle
#7
Line Kjær Winberg, Claus Henrik Nielsen, Søren Jacobsen
OBJECTIVES: To examine microparticles (MPs) from patients with SLE and healthy controls (HCs) by determining the cellular origin of the MPs, quantifying attached fragments of complement component 3 (C3) and assessing the ability of MPs to bind to circulating phagocytes and erythrocytes. These features may be relevant for clearance of MPs in SLE pathogenesis. METHODS: Attached C3 fragments (C3b, iC3b, C3d), membrane integrity and cell surface markers of MPs from 18 patients with SLE and 11 HCs were measured by adding specific antibodies, 7-aminoactinomycin D (7AAD) and annexin V...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/28398824/15-deoxy-%C3%A2-sup-12-14-sup-prostaglandin-j-sub-2-sub-exerts-pro-resolving-effects-through-nrf2-induced-expression-of-cd36-and-heme-oxygenase-1
#8
Wonki Kim, Ha-Na Lee, Jeong-Hoon Jang, Seung Hyeon Kim, Yeon-Hwa Lee, Young-Il Han, Hoang-Kieu-Chi Ngo, Yeonseo Choi, Yeonsoo Joe, Hun Taeg Chung, Yingqing Chen, Young-Nam Cha, Young-Joon Surh
. AIMS: 15-Deoxy-△<sup>12,14</sup>-prostaglandin J<sub>2</sub> (15d-PGJ2) has been shown to rescue cells from inflammatory insults and participate in the resolution of acute inflammation. In this study, we investigated molecular mechanisms underlying pro-resolving effects of 15d-PGJ2. RESULTS: 15d-PGJ2 injected into the peritoneum of mice facilitated the resolution of zymosan A-induced peritonitis. 15d-PGJ2 administration reduced the number of total leukocytes, and attenuated polymorphonuclear leukocytes infiltration...
March 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28369510/antagonistic-coevolution-of-mer-tyrosine-kinase-expression-and-function
#9
Amanda L Evans, Jack W D Blackburn, Kyle Taruc, Angela Kipp, Brennan S Dirk, Nina R Hunt, Stephen D Barr, Jimmy D Dikeakos, Bryan Heit
TYRO3, AXL, and MERTK (TAM) receptors are a family of receptor tyrosine kinases that maintain homeostasis through the clearance of apoptotic cells, and when defective, contribute to chronic inflammatory and autoimmune diseases such as atherosclerosis, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and Crohn's disease. In addition, certain enveloped viruses utilize TAM receptors for immune evasion and entry into host cells, with several viruses preferentially hijacking MERTK for these purposes...
March 23, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28359217/efferocytosis-induced-prostaglandin-e2-production-impairs-alveolar-macrophage-effector-functions-during-streptococcus-pneumoniae-infection
#10
Ana Cg Salina, Tais P Souza, Carlos H Serezani, Alexandra I Medeiros
Alveolar macrophages (AMs) are multitasking cells that maintain lung homeostasis by clearing apoptotic cells (efferocytosis) and performing antimicrobial effector functions. Different PRRs have been described to be involved in the binding and capture of non-opsonized Streptococcus pneumoniae, such as TLR-2, mannose receptor (MR) and scavenger receptors (SRs). However, the mechanism by which the ingestion of apoptotic cells negatively influences the clearance of non-opsonized S. pneumoniae remains to be determined...
April 2017: Innate Immunity
https://www.readbyqxmd.com/read/28325838/signaling-pathway-for-phagocyte-priming-upon-encounter-with-apoptotic-cells
#11
Saori Nonaka, Yuki Ando, Takuto Kanetani, Chiharu Hoshi, Yuji Nakai, Firzan Nainu, Kaz Nagaosa, Akiko Shiratsuchi, Yoshinobu Nakanishi
The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a Drosophila phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28322921/linking-deregulation-of-non-coding-rna-to-the-core-pathophysiology-of-alzheimer-s-disease-an-integrative-review
#12
REVIEW
Mark J Millan
The human genome encodes a vast repertoire of protein non-coding RNAs (ncRNA), some specific to the brain. MicroRNAs, which interfere with the translation of target mRNAs, are of particular interest since their deregulation has been implicated in neurodegenerative disorders like Alzheimer's disease (AD). However, it remains challenging to link the complex body of observations on miRNAs and AD into a coherent framework. Using extensive graphical support, this article discusses how a diverse panoply of miRNAs convergently and divergently impact (and are impacted by) core pathophysiological processes underlying AD: neuroinflammation and oxidative stress; aberrant generation of β-amyloid-42 (Aβ42); anomalies in the production, cleavage and post-translational marking of Tau; impaired clearance of Aβ42 and Tau; perturbation of axonal organisation; disruption of synaptic plasticity; endoplasmic reticulum stress and the unfolded protein response; mitochondrial dysfunction; aberrant induction of cell cycle re-entry; and apoptotic loss of neurons...
March 17, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28302404/mesenchymal-stem-cells-derived-mfg-e8-accelerates-diabetic-cutaneous-wound-healing
#13
Akihiko Uchiyama, Sei-Ichiro Motegi, Akiko Sekiguchi, Chisako Fujiwara, Buddhini Perera, Sachiko Ogino, Yoko Yokoyama, Osamu Ishikawa
BACKGROUND: Diabetic wounds are intractable due to complex factors, such as the inhibition of angiogenesis, dysfunction of phagocytosis by macrophages and abnormal inflammatory responses. It is recognized that mesenchymal stem cells (MSCs) promote wound healing in diabetic mice. We previously demonstrated that MSCs produce large amounts of MFG-E8. OBJECT: The objective was to ascertain the role of MSCs-derived MFG-E8 in murine diabetic wounds. METHODS: MFG-E8 WT/KO MSCs or rMFG-E8 were subcutaneously injected around the wound in diabetic db/db mice, and wound areas were analyzed...
March 6, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28272166/inhibition-of-myosin-light-chain-kinase-enhances-the-clearance-of-lipopolysaccharide-induced-lung-inflammation-possibly-by-accelerating-neutrophil-apoptosis
#14
Wei Shi, Chengyun Xu, Musaddique Hussain, Fugen Wu, Meiping Lu, Xiling Wu, Lanfang Tang, Ximei Wu, Junsong Wu
Neutrophils are a population of inflammatory cell involved in acute lung injury (ALI), and lipopolysaccharide (LPS) induced prolonged neutrophil survival and delayed neutrophil apoptosis hinder the alleviation of lung inflammation. Myosin light chain kinase (MLCK) involved the RhoA/Rho kinase signaling pathway responsible for the cytoskeletal arrangement, and previous studies have revealed that inhibition of MLCK induces apoptosis in vitro and in vivo. In this study, glycogen-induced neutrophils isolated from rats or mice were incubated with ML-7, a MLCK specific inhibitor, and LPS-induced ALI mice administrated with ML-7 were investigated, to demonstrate the roles of MLCK in neutrophils apoptosis as well as the possibility of which contributing to the clearance of inflammation...
March 7, 2017: Shock
https://www.readbyqxmd.com/read/28267881/distinctive-role-of-efferocytosis-in-dendritic-cell-maturation-and-migration-in-sterile-or-infectious-conditions
#15
Letícia de Aquino Penteado, Naiara Naiana Dejani, Felipe Fortino Verdan, Allan Botinhon Orlando, Victoria Ninõ, Fernanda De Nuzzi Dias, Ana Carolina Guerta Salina, Alexandra Ivo Medeiros
Efferocytosis, or clearance of apoptotic cells (ACs), by dendritic cells (DCs) leads to immune response suppression and tolerance to self-antigens. However, efferocytosis of infected cells (IACs) leads to the production of a mixed pro- and anti-inflammatory cytokine milieu. We examined the DC phenotype and ability to migrate after phagocytosis of ACs or IACs and observed higher levels of CD86 and CCR7 expression in DCs, as well as enhanced migration capacity following efferocytosis of infected cells. Interestingly, higher levels of IL-1β, IL-10 and PGE2 were also produced in this context...
March 7, 2017: Immunology
https://www.readbyqxmd.com/read/28266034/elevated-serum-mfg-e8-level-is-possibly-associated-with-the-presence-of-high-intensity-cerebral-lesions-on-magnetic-resonance-imaging-in-patients-with-systemic-lupus-erythematosus
#16
Chikako Kishi, Sei-Ichiro Motegi, Osamu Ishikawa
Human milk fat globule-EGF factor 8 (MFG-E8), also known as lactadherin, is a secreted glycoprotein that plays essential roles in the clearance of apoptotic cells and angiogenesis. It has been reported that serum MFG-E8 levels are higher in systemic lupus erythematosus (SLE) patients compared with in healthy controls; however, a previous study reported no correlation between serum MFG-E8 levels and SLE disease activity. The objective of this study was to assess serum MFG-E8 levels and their clinical associations in patients with SLE...
March 7, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28257077/functional-regulation-of-the-plasma-protein-histidine-rich-glycoprotein-by-zn-2-in-settings-of-tissue-injury
#17
REVIEW
Kristin M Priebatsch, Marc Kvansakul, Ivan K H Poon, Mark D Hulett
Divalent metal ions are essential nutrients for all living organisms and are commonly protein-bound where they perform important roles in protein structure and function. This regulatory control from metals is observed in the relatively abundant plasma protein histidine-rich glycoprotein (HRG), which displays preferential binding to the second most abundant transition element in human systems, Zinc (Zn(2+)). HRG has been proposed to interact with a large number of protein ligands and has been implicated in the regulation of various physiological and pathological processes including the formation of immune complexes, apoptotic/necrotic and pathogen clearance, cell adhesion, antimicrobial activity, angiogenesis, coagulation and fibrinolysis...
March 2, 2017: Biomolecules
https://www.readbyqxmd.com/read/28252646/porphyromonas-gingivalis-gingipains-cause-defective-macrophage-migration-towards-apoptotic-cells-and-inhibit-phagocytosis-of-primary-apoptotic-neutrophils
#18
Sowmya A Castro, Russell Collighan, Peter A Lambert, Irundika Hk Dias, Parbata Chauhan, Charlotte E Bland, Ivana Milic, Michael R Milward, Paul R Cooper, Andrew Devitt
Periodontal disease is a prevalent chronic inflammatory condition characterised by an aberrant host response to a pathogenic plaque biofilm resulting in local tissue damage and frustrated healing that can result in tooth loss. Cysteine proteases (gingipains) from the key periodontal pathogen Porphyromonas gingivalis have been implicated in periodontal disease pathogenesis by inhibiting inflammation resolution and are linked with systemic chronic inflammatory conditions such as rheumatoid arthritis. Efficient clearance of apoptotic cells is essential for the resolution of inflammation and tissue restoration...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28247940/plasma-membrane-calcium-atpase-4-pmca4-co-ordinates-calcium-and-nitric-oxide-signaling-in-regulating-murine-sperm-functional-activity
#19
Kristine E Olli, Kun Li, Deni S Galileo, Patricia A Martin-DeLeon
Reduced sperm motility (asthenospermia) and resulting infertility arise from deletion of the Plasma Membrane Ca(2+) -ATPase 4 (Pmca4) gene which encodes the highly conserved Ca(2+) efflux pump, PMCA4. This is the major Ca(2+) clearance protein in murine sperm. Since the mechanism underlying asthenospermia in PMCA4's absence or reduced activity is unknown, we investigated if sperm PMCA4 negatively regulates nitric oxide synthases (NOSs) and when absent NO, peroxynitrite, and oxidative stress levels are increased...
March 1, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28225631/conformational-changes-in-c-reactive-protein-affect-binding-to-curved-membranes-in-a-lipid-bilayer-model-of-the-apoptotic-cell-surface
#20
Aml A Alnaas, Carrie L Moon, Mitchell Alton, Scott M Reed, Michelle K Knowles
C-reactive protein (CRP) is a serum protein that binds to damaged membranes through a phosphatidylcholine binding site. The membrane binding process can initiate the complement immune response and facilitates the clearance of apoptotic cells, likely aiding in the protection of autoimmunity. The initiation of an immune response relies on a conformation change from a native, pentameric form to a modified form, where the modified form binds complement proteins (i.e., C1q) and regulatory proteins substantially better than the native form...
March 30, 2017: Journal of Physical Chemistry. B
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