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Clearance of apoptotic cells

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https://www.readbyqxmd.com/read/29150239/tissue-resident-macrophages-are-locally-programmed-for-silent-clearance-of-apoptotic-cells
#1
Allison W Roberts, Bettina L Lee, Jacques Deguine, Shinu John, Mark J Shlomchik, Gregory M Barton
Although apoptotic cells (ACs) contain nucleic acids that can be recognized by Toll-like receptors (TLRs), engulfment of ACs does not initiate inflammation in healthy organisms. Here we identified macrophage populations that continually engulf ACs in distinct tissues and found that these macrophages share characteristics compatible with immunologically silent clearance of ACs; such characteristics include high expression of AC recognition receptors, low expression of TLR9, and reduced TLR responsiveness to nucleic acids...
November 13, 2017: Immunity
https://www.readbyqxmd.com/read/29144198/development-of-novel-fluorescent-particles-applicable-for-phagocytosis-assays-with-human-macrophages
#2
Cecilia Sóñora, Paula Arbildi, Iris Miraballes-Martínez, Ana Hernández
Phagocytosis is a fundamental process for removal of pathogens and for clearance of apoptotic cells. The objective of this work was the preparation of fluorescent microspheres by a simple method and the evaluation of its applicability in phagocytosis assays by using different human derived cells, differentiated THP-1 cell line and blood monocytes, with flow cytometry measurements for functionality assays. Our results show that microparticles are efficiently internalized in a non-opsonized form and in dose dependent manner by both cellular types...
November 16, 2017: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/29134671/macrophage-roles-in-the-clearance-of-apoptotic-cells-and-control-of-inflammation-in-the-prostate-gland-after-castration
#3
Juliete A F Silva, Alexandre Bruni-Cardoso, Taize M Augusto, Danilo M Damas-Souza, Guilherme O Barbosa, Sérgio L Felisbino, Dagmar R Stach-Machado, Hernandes F Carvalho
BACKGROUND: Androgen deprivation results in massive apoptosis in the prostate gland. Macrophages are actively engaged in phagocytosing epithelial cell corpses. However, it is unknown whether microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis (LAP) is involved and contribute to prevent inflammation. METHODS: Flow cytometry, RT-PCR and immunohistochemistry were used to characterize the macrophage subpopulation residing in the epithelial layer of the rat ventral prostate (VP) after castration...
November 14, 2017: Prostate
https://www.readbyqxmd.com/read/29121034/the-impact-of-advanced-opioid-drugs-and-analgesic-adjuvants-on-murine-macrophage-oxygen-burst
#4
Michael Kozlowski, Katarzyna Nazimek, Magdalena Wąsik, Iwona Filipczak-Bryniarska, Krzysztof Bryniarski
Macrophages (Mf) are a versatile group of phagocytic cells responsible for fulfilling a variety of immune functions, most notably for mounting the initial anti-microbial response and for the clearance of cellular debris and apoptotic bodies. The key processes for fulfilling these functions include the production of reactive oxygen intermediates (ROIs) and nitric oxide (NO). Mf also express a variety of receptors, including opioid, serotonin, and norepinephrine receptors, and thus can react to various substances...
2017: Folia Medica Cracoviensia
https://www.readbyqxmd.com/read/29118755/apoptotic-cells-induced-signaling-for-immune-homeostasis-in-macrophages-and-dendritic-cells
#5
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/29116131/context-dependent-compensation-among-phosphatidylserine-recognition-receptors
#6
Kristen K Penberthy, Claudia Rival, Laura S Shankman, Michael H Raymond, Jianye Zhang, Justin S A Perry, Chang Sup Lee, Claudia Z Han, Suna Onengut-Gumuscu, Krzysztof Palczewski, Jeffrey J Lysiak, Kodi S Ravichandran
Phagocytes express multiple phosphatidylserine (PtdSer) receptors that recognize apoptotic cells. It is unknown whether these receptors are interchangeable or if they play unique roles during cell clearance. Loss of the PtdSer receptor Mertk is associated with apoptotic corpse accumulation in the testes and degeneration of photoreceptors in the eye. Both phenotypes are linked to impaired phagocytosis by specialized phagocytes: Sertoli cells and the retinal pigmented epithelium (RPE). Here, we overexpressed the PtdSer receptor BAI1 in mice lacking MerTK (Mertk (-/-) Bai1 (Tg) ) to evaluate PtdSer receptor compensation in vivo...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29109724/actors-and-factors-in-the-resolution-of-intestinal-inflammation-lipid-mediators-as-a-new-approach-to-therapy-in-inflammatory-bowel-diseases
#7
REVIEW
Federica Ungaro, Federica Rubbino, Silvio Danese, Silvia D'Alessio
In the last few decades, the pathogenesis of inflammatory bowel disease (IBD) in genetically predisposed subjects susceptible to specific environmental factors has been attributed to disturbance of both the immune and non-immune system and/or to the imbalanced interactions with microbes. However, increasing evidences support the idea that defects in pro-resolving pathways might strongly contribute to IBD onset. The resolution of inflammation is now recognized as a dynamic event coordinated by specialized pro-resolving lipid mediators (LMs), which dampen inflammation-sustaining events, such as angiogenesis, release of pro-inflammatory cytokines, clearance of apoptotic cells, and microorganisms...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29107169/the-complement-system-is-dysfunctional-in-metabolic-disease-evidences-in-plasma-and-adipose-tissue-from-obese-and-insulin-resistant-subjects
#8
REVIEW
José María Moreno-Navarrete, José Manuel Fernández-Real
The relationship between chronic low-grade inflammation, insulin resistance and other obesity-associated metabolic disturbances is increasingly recognized. The possible mechanisms that trigger these immunologic alterations remain to be fully understood. The complement system is a crucial element of immune defense system, being important in the activation of innate and adaptative immune response, promoting the clearance of apoptotic and damaged endogenous cells and participating in processes of tissue development, degeneration, and regeneration...
October 26, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29106805/innate-immunity-and-neurodegeneration
#9
Larisa I Labzin, Michael T Heneka, Eicke Latz
The innate immune system plays diverse roles in health and disease. It represents the first line of defense against infection and is involved in tissue repair, wound healing, and clearance of apoptotic cells and cellular debris. Excessive or nonresolving innate immune activation can lead to systemic or local inflammatory complications and cause or contribute to the development of inflammatory diseases. In the brain, microglia represent the key innate immune cells, which are involved in brain development, brain maturation, and homeostasis...
November 6, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/29100097/monogenic-lupus-it-s-all-new
#10
REVIEW
Patricia Costa-Reis, Kathleen E Sullivan
Monogenic lupus is rare, but its study has contributed immensely to a better understanding of the pathogenesis of systemic lupus erythematosus. The first forms identified were inherited complement deficiencies, which predisposed to lupus due to impaired tolerance, and aberrant clearance of apoptotic bodies and immune complexes. In recent years, several new monogenic disorders with a lupus-like phenotype have been described. These include forms that affect nucleic acid repair, degradation and sensing (TREX1, DNASE1L3), the type I interferon (IFN) pathway (SAMHD1, RNASEH2ABC, ADAR1, IFIH1, ISG15, ACP5, TMEM173) and B cell development checkpoints (PRKCD; RAG2)...
October 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29062314/harnessing-apoptotic-cell-clearance-to-treat-autoimmune-arthritis
#11
REVIEW
Philippe Saas, Francis Bonnefoy, Eric Toussirot, Sylvain Perruche
Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell transplantation to prevent graft-versus-host disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29061768/cutting-edge-anti-tim-3-treatment-exacerbates-pulmonary-inflammation-and-fibrosis-in-mice
#12
Takuma Isshiki, Hisaya Akiba, Masafumi Nakayama, Norihiro Harada, Ko Okumura, Sakae Homma, Sachiko Miyake
Promising results of immune checkpoint inhibitors have indicated the use of immunotherapy against malignant tumors. However, they cause serious side effects, including autoimmune diseases and pneumonitis. T cell Ig and mucin domain (TIM)-3 is a new candidate immune checkpoint molecule; however, the potential toxicity associated with anti-TIM-3 treatment is unknown. In this study, we investigated the pathological contribution of anti-TIM-3 mAb in a bleomycin-induced lung inflammation and fibrosis model. Anti-TIM-3-treated mice showed more severe inflammation and peribronchiolar fibrosis compared with control IgG-treated mice...
October 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29027226/efferocytosis-of-dying-cells-differentially-modulate-immunological-outcomes-in-tumor-microenvironment
#13
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/28983582/effects-of-tripterygium-glycoside-treatment-on-experimental-autoimmune-encephalomyelitis
#14
Jianmin Qiu, Xuelian You, Gang Wu
Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease mediated by CD4+ T cells. It is characterized by mononuclear cell infiltration around the small blood vessels in the central nervous system (CNS). Previous investigations have found that apoptosis is associated with the occurrence and development of autoimmune disease, and that mononuclear cell apoptosis and clearance from the CNS is one of the repair mechanisms of EAE. Tripterygium wilfordii glycoside (TWP) is an organic matter isolated from Tripterygium wilfordii, which has anti‑inflammatory and immunosuppressive effects...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28978108/tunicamycin-induced-endoplasmic-reticulum-stress-promotes-apoptosis-of-prostate-cancer-cells-by-activating-mtorc1
#15
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...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28942921/mitochondrial-fission-promotes-the-continued-clearance-of-apoptotic-cells-by-macrophages
#16
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/28928467/cross-talk-between-mir-471-5p-and-autophagy-component-proteins-regulates-lc3-associated-phagocytosis-lap-of-apoptotic-germ-cells
#17
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
#18
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
#19
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
#20
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
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