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Clearance of apoptotic cells

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https://www.readbyqxmd.com/read/28928467/cross-talk-between-mir-471-5p-and-autophagy-component-proteins-regulates-lc3-associated-phagocytosis-lap-of-apoptotic-germ-cells
#1
Subbarayalu Panneerdoss, Suryavathi Viswanadhapalli, Nourhan Abdelfattah, Benjamin C Onyeagucha, Santosh Timilsina, Tabrez A Mohammad, Yidong Chen, Michael Drake, Kristiina Vuori, T Rajendra Kumar, Manjeet K Rao
Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28919893/ripk3-fas-associated-death-domain-axis-regulates-pulmonary-immunopathology-to-cryptococcal-infection-independent-of-necroptosis
#2
Zhenzong Fa, Qun Xie, Wei Fang, Haibing Zhang, Haiwei Zhang, Jintao Xu, Weihua Pan, Jinhua Xu, Michal A Olszewski, Xiaoming Deng, Wanqing Liao
Fas-associated death domain (FADD) and receptor interacting protein kinase 3 (RIPK3) are multifunctional regulators of cell death and immune response. Using a mouse model of cryptococcal infection, the roles of FADD and RIPK3 in anti-cryptococcal defense were investigated. Deletion of RIPK3 alone led to increased inflammatory cytokine production in the Cryptococcus neoformans-infected lungs, but in combination with FADD deletion, it led to a robust Th1-biased response with M1-biased macrophage activation. Rather than being protective, these responses led to paradoxical C...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878781/calreticulin-release-at-an-early-stage-of-death-modulates-the-clearance-by-macrophages-of-apoptotic-cells
#3
Rim Osman, Pascale Tacnet-Delorme, Jean-Philippe Kleman, Arnaud Millet, Philippe Frachet
Calreticulin (CRT) is a well-known "eat-me" signal harbored by dying cells participating in their recognition by phagocytes. CRT is also recognized to deeply impact the immune response to altered self-cells. In this study, we focus on the role of the newly exposed CRT following cell death induction. We show that if CRT increases at the outer face of the plasma membrane and is well recognized by C1q even when phosphatidylserine is not yet detected, CRT is also released in the surrounding milieu and is able to interact with phagocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28861421/the-role-of-reactive-oxygen-species-in-myocardial-redox-signaling-and-regulation
#4
REVIEW
Demetrios Moris, Michael Spartalis, Eleni Tzatzaki, Eleftherios Spartalis, Georgia-Sofia Karachaliou, Andreas S Triantafyllis, Georgios I Karaolanis, Diamantis I Tsilimigras, Stamatios Theocharis
Reactive oxygen species (ROS) are subcellular messengers in gene regulatory and signal transduction pathways. In pathological situations, ROS accumulate due to excessive production or insufficient degradation, leading to oxidative stress (OS). OS causes oxidation of DNA, membranes, cellular lipids, and proteins, impairing their normal function and leading ultimately to cell death. OS in the heart is increased in response to ischemia/reperfusion, hypertrophy, and heart failure. The concentration of ROS is determined by their rates of production and clearance by antioxidants...
August 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28854431/involvement-of-s100a8-a9-tlr4-nlrp3-inflammasome-pathway-in-contrast-induced-acute-kidney-injury
#5
Xuexian Tan, Xiaohe Zheng, Zena Huang, Jiaqiong Lin, Chuli Xie, Yan Lin
BACKGROUND: Contrast-induced acute kidney injury (CIAKI) is a common cause of hospital-acquired acute kidney injury (AKI). S100A8/A9-TLR4-NLRP3 inflammasome pathway triggers inflammation, apoptosis and tissue injury in several AKI models. Nevertheless, the underlying mechanism of S100A8/A9-TLR4-NLRP3 inflammasome pathway in CIKAI is not clear. We aimed to investigate the possible role of S100A8/A9-TLR4-NLRP3 inflammasome in the pathophysiology of CIAKI. METHODS: We treated male rats and NRK-52E cells by iopromide to establish in vivo and in vitro models of CIAKI...
August 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28851810/mertk-cleavage-on-resident-cardiac-macrophages-compromises-repair-after-myocardial-ischemia-reperfusion-injury
#6
Matthew DeBerge, Xin-Yi Yeap, Shirley Dehn, Shuang Zhang, Lubov S Grigoryeva, Sol Misener, Daniele Procissi, Xin Zhou, Daniel C Lee, William A Muller, Xunrong Luo, Carla Rothlin, Ira Tabas, Edward B Thorp
Rationale: Clinical benefits of reperfusion after myocardial infarction (MI) are offset by maladaptive innate immune cell function and therapeutic interventions are lacking. Objective: We sought to test the significance of phagocytic clearance by resident and recruited phagocytes after myocardial ischemia reperfusion (I/R). Methods and Results: In humans, we discovered that clinical reperfusion after MI led to significant elevation of the soluble form of MerTK (i.e. solMER), a critical biomarker of compromised phagocytosis by innate macrophages...
August 29, 2017: Circulation Research
https://www.readbyqxmd.com/read/28806274/transfusion-related-immunomodulation-a-reappraisal
#7
Lyla A Youssef, Steven L Spitalnik
PURPOSE OF REVIEW: This review summarizes current and prior observations regarding transfusion-related immunomodulation (TRIM) and puts these ideas into a modern immunological context, incorporating concepts from innate, adaptive, and nutritional immunity. We propose that TRIM research focus on determining whether there are specific, well-defined immunosuppressive effects from transfusing 'pure' red blood cells (RBCs) themselves, along with the by-products produced by the stored RBCs as a result of the 'storage lesion...
August 12, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28796886/macrophage-metabolism-in-atherosclerosis
#8
REVIEW
Gael F P Bories, Norbert Leitinger
A key aspect of atherosclerosis is the maladaptive inflammatory response to lipoprotein accumulation in the artery. The failure to decrease lipid accumulation, to clear apoptotic cells and to resolve inflammation ultimately leads to macrophage accumulation within the vascular wall(1,2,3,4) . Several subsets of macrophages are found inside atherosclerotic plaques(5,6,7) : Pro-inflammatory M1-like macrophages potentially participate in atherosclerosis initiation and progression; M2-like macrophages are thought to be protective due to their anti-inflammatory and profibrotic properties, presumably stabilizing the plaque(8,9;) Mox macrophages develop in response to oxidized phospholipids and present a glutathione- and potentially redox-regulating phenotype(10) ; Mhem macrophages are found in areas of plaque hemorrhage(11,12) where they are involved in heme clearance...
August 10, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28767064/psoralea-corylifolia-l-seed-extract-attenuates-diabetic-nephropathy-by-inhibiting-renal-fibrosis-and-apoptosis-in-streptozotocin-induced-diabetic-mice
#9
Eunhui Seo, Hwansu Kang, Yoon Sin Oh, Hee-Sook Jun
The Psoralea corylifolia L. seed (PCS) is a widely used herbal medicine, but its possible effect against diabetic nephropathy has not been studied. To investigate the anti-nephropathic effect of PCS extracts, we performed experiments using a diabetic mouse model and high glucose-treated mesangial cells. Streptozotocin (STZ)-induced diabetic mice were orally administered PCS extract for 8 weeks (500 mg/kg/day). Increased creatinine clearance, urine volume, urine microalbumin, and mesangial expansion were observed in STZ-induced diabetic mice; these were significantly reduced by PCS extract administration...
August 2, 2017: Nutrients
https://www.readbyqxmd.com/read/28754872/tunicamycin-induced-endoplasmic-reticulum-stress-promotes-apoptosis-of-prostate-cancer-cells-by-activating-mtorc1
#10
Prasun Guha, Engin Kaptan, Padmaja Gade, Dhananjaya V Kalvakolanu, Hafiz Ahmed
Studies suggest that tunicamycin may work as a therapeutic drug to cancer cells by inducing stress in the endoplasmic reticulum (ER) through unfolded protein response (UPR) and thereby promoting apoptosis. However, mechanisms of the prolonged activation of the UPR under sustained ER stress in the regulation of cell apoptosis are largely unknown. To delineate the role of candidate genes in the apoptotic process under ER stress and to search for new therapeutic strategies to treat metastatic castration resistant prostate cancer, we performed whole genome expression microarray analysis in tunicamycin treated metastatic androgen-insensitive prostate cancer cells, PC-3...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28754800/frontline-science-tim-3-mediated-dysfunctional-engulfment-of-apoptotic-cells-in-sle
#11
Di Zhao, Min Guo, Bing Liu, Qinghai Lin, Tingting Xie, Qianqian Zhang, Xiaoxia Jia, Qiang Shu, Xiaohong Liang, Lifen Gao, Chunhong Ma
T cell Ig and mucin domain-containing molecule 3 (Tim-3) has been found to play important roles in autoimmune diseases, but whether Tim-3-mediated engulfment of apoptotic cells is involved in systemic lupus erythematosus (SLE) remains to be elucidated. In this study, we verified the role of human Tim-3 (hTim-3) as the receptor of phosphatidylserine (PS) in human embryonic kidney (HEK)293 cells, which initiated the engulfment of apoptotic cells. Both IgV and the mucin domain of Tim-3 were crucial in the phagocytosis of apoptotic cells, and there existed the key cytoplasmic domain for signal transduction...
July 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28752081/absence-of-nucleotide-oligomerization-domain-2-is-associated-with-less-distinct-disease-in-campylobacter-jejuni-infected-secondary-abiotic-il-10-deficient-mice
#12
Markus M Heimesaat, Ursula Grundmann, Marie E Alutis, André Fischer, Stefan Bereswill
Human Campylobacter jejuni-infections are progressively increasing worldwide. Despite their high prevalence and socioeconomic impact the underlying mechanisms of pathogen-host-interactions are only incompletely understood. Given that the innate immune receptor nucleotide-oligomerization-domain-2 (Nod2) is involved in clearance of enteropathogens, we here evaluated its role in murine campylobacteriosis. To address this, we applied Nod2-deficient IL-10(-/-) (Nod2(-/-) IL-10(-/-)) mice and IL-10(-/-) counterparts both with a depleted intestinal microbiota to warrant pathogen-induced enterocolitis...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28710749/express-fret-labeling-and-analysis-of-phagocytic-clearance
#13
Vladimir V Didenko
Lysosomal DNase II in phagocytic digestion produces DNA ends with 3'PO4/5'OH, which differ from those created in apoptotic DNA fragmentation, and can be used to label phagocytic clearance of cell death. Here, we describe the use of these specific DNA ends as selective markers of phagocytic reaction in cell suspensions. The approach does not require cell fixation. It selectively labels blunt-ended DNA breaks with terminal 5'OH. The detection is performed by ultra-fast FRET probes in a single step, closed-tube procedure...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28697439/targeting-dendritic-cells-for-the-treatment-of-autoimmune-disorders
#14
REVIEW
C Sousa, I Pereira, A C Santos, C Carbone, A B Kovačević, A M Silva, E B Souto
In the last decades, it has been recognized that extracellular vesicles (EVs) are not only cell debris with no biological role, but instead they play a key role in information exchange between cells either in health and disease conditions. EVs exhibit indeed their biological role in a pleiotropic manner. They can modulate immune responses through the activation, transfer or removal of surface receptors on target cells, the removal of cytolytic components such as membrane attack complexes, and the transfer of signaling molecules/effectors, such as nucleic acid species, infectious particles, and oncogenes...
June 30, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28696256/a-novel-subset-of-anti-inflammatory-cd138-macrophages-is-deficient-in-mice-with-experimental-lupus
#15
Shuhong Han, Haoyang Zhuang, Stepan Shumyak, Jingfan Wu, Hui Li, Li-Jun Yang, Westley H Reeves
Dead cells accumulating in the tissues may contribute to chronic inflammation. We examined the cause of impaired apoptotic cell clearance in human and murine lupus. Dead cells accumulated in bone marrow from lupus patients but not from nonautoimmune patients undergoing myeloablation, where they were efficiently removed by macrophages (MΦ). Impaired apoptotic cell uptake by MΦ also was seen in mice treated i.p. with pristane (develop lupus) but not mineral oil (MO) (do not develop lupus). The inflammatory response to both pristane and MO rapidly depleted resident (Tim4(+)) large peritoneal MΦ...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28694452/phosphatidylserine-mediated-platelet-clearance-by-endothelium-decreases-platelet-aggregates-and-procoagulant-activity-in-sepsis
#16
Ruishuang Ma, Rui Xie, Chengyuan Yu, Yu Si, Xiaoming Wu, Lu Zhao, Zhipeng Yao, Shaohong Fang, He Chen, Valerie Novakovic, Chunyan Gao, Junjie Kou, Yayan Bi, Hemant S Thatte, Bo Yu, Shufen Yang, Jin Zhou, Jialan Shi
The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28686604/boosting-efferocytosis-in-alveolar-space-using-bcg-vaccine-to-protect-host-against-influenza-pneumonia
#17
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/28686526/in-life-there-is-death-how-epithelial-tissue-barriers-are-preserved-despite-the-challenge-of-apoptosis
#18
Kinga Duszyc, Guillermo A Gomez, Kate Schroder, Matthew J Sweet, Alpha S Yap
Apoptosis is a ubiquitous mode of programmed cell death that is found in healthy organs and can be stimulated by many toxic stresses. When it occurs in epithelia, apoptosis presents major challenges to tissue integrity. Apoptotic corpses can promote inflammatory and autoimmune responses if they are retained, and the cellular fragmentation that accompanies apoptosis can potentially compromise the epithelial barrier. Here we discuss 2 homeostatic mechanisms that allow epithelia to circumvent these potential risks: clearance of apoptotic corpses by professional and non-professional phagocytes and physical expulsion of apoptotic cells by apical extrusion...
June 28, 2017: Tissue Barriers
https://www.readbyqxmd.com/read/28680391/the-role-of-the-multifunctional-bag3-protein-in-cellular-protein-quality-control-and-in-disease
#19
REVIEW
Elisabeth Stürner, Christian Behl
In neurons, but also in all other cells the complex proteostasis network is monitored and tightly regulated by the cellular protein quality control (PQC) system. Beyond folding of newly synthesized polypeptides and their refolding upon misfolding the PQC also manages the disposal of aberrant proteins either by the ubiquitin-proteasome machinery or by the autophagic-lysosomal system. Aggregated proteins are primarily degraded by a process termed selective macroautophagy (or aggrephagy). One such recently discovered selective macroautophagy pathway is mediated by the multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28671983/isoflurane-promotes-phagocytosis-of-apoptotic-neutrophils-through-ampk-mediated-adam17-mer-signaling
#20
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
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