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Efferocytosis

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https://www.readbyqxmd.com/read/28720835/exophagy-of-annexin-a2-via-rab11-rab8a-and-rab27a-in-ifn-%C3%AE-stimulated-lung-epithelial-cells
#1
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
#2
Anusha N Seneviratne, Andreas O Edsfeldt, Jennifer E Cole, Christina Kassiteridi, Maarten Swart, Inhye Park, Patricia Green, Tariq E Khoyratty, David G 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 two complementary models...
July 11, 2017: Circulation
https://www.readbyqxmd.com/read/28686604/boosting-efferocytosis-in-alveolar-space-using-bcg-vaccine-to-protect-host-against-influenza-pneumonia
#3
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
#4
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
#5
Peter M Henson
In metazoa, 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...
June 14, 2017: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/28605477/mertk-as-a-therapeutic-target-in-glioblastoma
#6
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
#7
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 wk old male C57BL/6J mice were treated with trabectedin - a chemotherapeutic with established anti-macrophage effects...
June 10, 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
#8
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
https://www.readbyqxmd.com/read/28536576/implication-of-apoptosis-for-the-pathogenesis-of-trypanosoma-cruzi-infection
#9
REVIEW
Débora Decote-Ricardo, Marise P Nunes, Alexandre Morrot, Celio G Freire-de-Lima
Apoptosis is induced during the course of immune response to different infectious agents, and the ultimate fate is the recognition and uptake of apoptotic bodies by neighboring cells or by professional phagocytes. Apoptotic cells expose specific ligands to a set of conserved receptors expressed on macrophage cellular surface, which are the main cells involved in the clearance of the dying cells. These scavenger receptors, besides triggering the production of anti-inflammatory factors, also block the production of inflammatory mediators by phagocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28513416/the-role-of-esx-1-in-mycobacterium-tuberculosis-pathogenesis
#10
Ka-Wing Wong
In this article, we have described several cellular pathological effects caused by the Mycobacterium tuberculosis ESX-1. The effects include induction of necrosis, NOD2 signaling, type I interferon production, and autophagy. We then attempted to suggest that these pathological effects are mediated by the cytosolic access of M. tuberculosis-derived materials as a result of the phagosome-disrupting activity of the major ESX-1 substrate ESAT-6. Such activity of ESAT-6 is most likely due to its pore-forming activity at the membrane...
May 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28473436/dba-2j-haplotype-on-distal-chromosome-2-reduces-mertk-expression-restricts-efferocytosis-and-increases-susceptibility-to-atherosclerosis
#11
COMPARATIVE STUDY
Yukako Kayashima, Natalia Makhanova, Nobuyo Maeda
OBJECTIVE: Arch atherosclerosis 4 (Aath4) is a quantitative trait locus for atherosclerotic plaque formation in the inner curve of the aortic arch previously identified in an F2 cross of Apoe(-/-) mice on DBA/2J and 129S6 backgrounds. C-mer proto-oncogene tyrosine kinase (Mertk), coding for a ligand-activated transmembrane tyrosine kinase, is a candidate gene within the same chromosomal region. Our objective was to determine whether strain differences in Mertk influence plaque formation...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28471261/rab17-mediates-intermixing-of-phagocytosed-apoptotic-cells-with-recycling-endosomes
#12
Charles Yin, Dean Argintaru, Bryan Heit
Efferocytosis-the phagocytic removal of apoptotic cells-is required for preventing the presentation of apoptotic cell-derived antigens. This process is regulated by Rab17-dependent sorting of efferocytosed cargos from the phagolysosome to recycling endosomes. In this study we demonstrate that Rab17 is rapidly recruited to efferosomes, followed by migration of the efferosome to the cell center where it intermixes with lysosomes and undergoes Rab17-dependent vesiculation. These efferosome-derived vesicles then traffic in a Rab17-dependent manner to the cell periphery, where they transfer cargo to recycling endosomes...
May 4, 2017: Small GTPases
https://www.readbyqxmd.com/read/28457196/immunomodulation-in-systemic-lupus-erythematosus-induction-of-m2-population-in-monocyte-derived-macrophages-by-pioglitazone
#13
S Mohammadi, M Saghaeian-Jazi, S Sedighi, A Memarian
Macrophages have recently gained attention in systemic lupus erythematosus (SLE) pathogenesis for their role in the anti-inflammatory clearance of apoptotic cells. The M1/M2 polarization of macrophages improves efferocytic capability. Peroxisome proliferator-activated receptor γ is proposed to function in the expansion of the M2 subpopulation. Pioglitazone is a peroxisome proliferator-activated receptor γ agonist with a variety of anti-inflammatory effects. In this paper, we investigated the ex vivo alterations of monocyte-derived macrophages of 15 newly diagnosed SLE patients and 10 normal subjects triggered by apoptotic cells among SLE patients following pioglitazone treatment...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28455714/macrophage-dysfunction-in-respiratory-disease
#14
Kylie B R Belchamber, Louise E Donnelly
In the healthy lung, macrophages maintain homeostasis by clearing inhaled particles, bacteria, and removing apoptotic cells from the local pulmonary environment. However, in respiratory diseases including chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis, macrophages appear to be dysfunctional and may contribute to disease pathogenesis. In COPD, phagocytosis of bacterial species and apoptotic cells by both alveolar macrophages and monocyte-derived macrophages is significantly reduced, leading to colonization of the lung with pathogenic bacteria...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28448535/alpha-1-antitrypsin-supplementation-improves-alveolar-macrophages-efferocytosis-and-phagocytosis-following-cigarette-smoke-exposure
#15
Karina A Serban, Daniela N Petrusca, Andrew Mikosz, Christophe Poirier, Angelia D Lockett, Lauren Saint, Matthew J Justice, Homer L Twigg, Michael A Campos, Irina Petrache
Cigarette smoking (CS), the main risk factor for COPD (chronic obstructive pulmonary disease) in developed countries, decreases alveolar macrophages (AM) clearance of both apoptotic cells and bacterial pathogens. This global deficit of AM engulfment may explain why active smokers have worse outcomes of COPD exacerbations, episodes characterized by airway infection and inflammation that carry high morbidity and healthcare cost. When administered as intravenous supplementation, the acute phase-reactant alpha-1 antitrypsin (A1AT) reduces the severity of COPD exacerbations in A1AT deficient (AATD) individuals and of bacterial pneumonia in murine models, but the effect of A1AT on AM scavenging functions has not been reported...
2017: PloS One
https://www.readbyqxmd.com/read/28428217/microrna-33-regulates-macrophage-autophagy-in-atherosclerosis
#16
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...
June 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28412392/diminished-airway-macrophage-expression-of-the-axl-receptor-tyrosine-kinase-is-associated-with-defective-efferocytosis-in-asthma
#17
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
No abstract text is available yet for this article.
April 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28407017/characterizing-the-anti-inflammatory-and-tissue-protective-actions-of-a-novel-annexin-a1-peptide
#18
Mauro Perretti, Clara Di Filippo, Michele D'Amico, Jesmond Dalli
Inflammation in now appreciated to be at the centre of may diseases that affect Western civilization. Current therapeutics for managing these conditions may interfere with the host response leading to immune suppression. We recently developed an annexin (Anx) A1-derived peptide, coined CR-AnxA12-50, which displays potent pro-resolving and tissue protective actions. Herein, we designed a novel peptide using CR-AnxA12-50 as a template that was significantly more resistant to neutrophil-mediated degradation. This peptide, termed CR-AnxA12-48, retained high affinity and specificity to the pro-resolving Lipoxin A4 receptor (ALX) with an IC50 of ~20nM...
2017: PloS One
https://www.readbyqxmd.com/read/28398824/15-deoxy-%C3%AE-12-14-prostaglandin-j2-exerts-proresolving-effects-through-nuclear-factor-e2-related-factor-2-induced-expression-of-cd36-and-heme-oxygenase-1
#19
Wonki Kim, Ha-Na Lee, Jeong-Hoon Jang, Seung Hyeon Kim, Yeon-Hwa Lee, Young-Il Hahn, Hoang-Kieu-Chi Ngo, Yeonseo Choi, Yeonsoo Joe, Hun Taeg Chung, Yingqing Chen, Young Nam Cha, Young-Joon Surh
AIMS: 15-Deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) has been shown to rescue cells from inflammatory insults and to participate in the resolution of acute inflammation. In this study, we investigated molecular mechanisms underlying proresolving 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 leukocyte infiltration...
May 12, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28376111/coordinated-balance-of-rac1-and-rhoa-plays-key-roles-in-determining-phagocytic-appetite
#20
Sang-Yeob Kim, Soyoun Kim, Dong-Jun Bae, Seung-Yoon Park, Ga-Young Lee, Gyeong-Min Park, In-San Kim
The removal of unwanted or damaged cells by phagocytes is achieved via a finely regulated cleaning process called efferocytosis. To characterize the mechanisms through which phagocytes control the intake of apoptotic cells, we investigated how the phagocyte's appetite for engulfed cells may be coordinated by RhoA and Rac1 in the phagocytic cup. We used FRET biosensors to visualize the spatiotemporal dynamics of Rho-family GTPases, and found that RhoA, which is known to be downregulated during phagocytosis, was transiently upregulated at the phagocytic cup immediately prior to ingestion...
2017: PloS One
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