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Efferocytosis

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https://www.readbyqxmd.com/read/28513416/the-role-of-esx-1-in-mycobacterium-tuberculosis-pathogenesis
#1
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
#2
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. 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. APPROACH AND RESULTS: To dissect the strain effects of Mertk on atherosclerosis, we first established a congenic mouse line (Aath4a(DBA/DBA) ) in which a 5' region of Aath4 of DBA/2J, including Mertk, was backcrossed onto a 129S6-Apoe(-/-) background...
May 4, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28471261/rab17-mediates-intermixing-of-phagocytosed-apoptotic-cells-with-recycling-endosomes
#3
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
#4
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
#5
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
#6
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
#7
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/28412392/diminished-airway-macrophage-expression-of-the-axl-receptor-tyrosine-kinase-is-associated-with-defective-efferocytosis-in-asthma
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28359217/efferocytosis-induced-prostaglandin-e2-production-impairs-alveolar-macrophage-effector-functions-during-streptococcus-pneumoniae-infection
#12
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/28333143/molecular-insights-of-gas6-tam-in-cancer-development-and-therapy
#13
REVIEW
Guiling Wu, Zhiqiang Ma, Wei Hu, Dongjin Wang, Bing Gong, Chongxi Fan, Shuai Jiang, Tian Li, Jianyuan Gao, Yang Yang
Since growth arrest-specific gene 6 (Gas6) was discovered in 1988, numerous studies have highlighted the role of the Gas6 protein and its receptors Tyro3, Axl and Mer (collectively referred to as TAM), in proliferation, apoptosis, efferocytosis, leukocyte migration, sequestration and platelet aggregation. Gas6 has a critical role in the development of multiple types of cancers, including pancreatic, prostate, oral, ovarian and renal cancers. Acute myelocytic leukaemia (AML) is a Gas6-dependent cancer, and Gas6 expression predicts poor prognosis in AML...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28320709/plasmin-and-plasminogen-induce-macrophage-reprogramming-and-regulate-key-steps-of-inflammation-resolution-via-annexin-a1
#14
Michelle A Sugimoto, Ana Luíza C Ribeiro, Bruno R C Costa, Juliana P Vago, Kátia M Lima, Fernanda S Carneiro, Mylena Maira O Ortiz, Graziele Letícia N Lima, Aline A F Carmo, Renata M Rocha, Denise A Perez, Alessandra C Reis, Vanessa Pinho, Lindsey A Miles, Cristiana C Garcia, Mauro M Teixeira, Lirlândia P Sousa
Inflammation resolution is an active process that functions to restore tissue homeostasis. Participation of the plasminogen/plasmin (Plg/Pla) system in the productive phase of inflammation is well known, but its involvement in the resolution phase remains unclear. Therefore, we aimed to investigate the potential role of Plg/Pla in key events during the resolution of acute inflammation and its underlying mechanisms. Plg/Pla injection into the pleural cavity of BALB/c mice induced a time-dependent influx of mononuclear cells that were primarily macrophages of anti-inflammatory (M2 - F4/80(high) Gr1(-) CD11b(high)) and proresolving (Mres - F4/80(med) CD11b(low)) phenotypes, without changing the number of macrophages with a pro-inflammatory profile (M1 - F4/80(low) Gr1(+) CD11b(med))...
March 20, 2017: Blood
https://www.readbyqxmd.com/read/28292945/from-leukocyte-recruitment-to-resolution-of-inflammation-the-cardinal-role-of-integrins
#15
REVIEW
Ioannis Kourtzelis, Ioannis Mitroulis, Janusz von Renesse, George Hajishengallis, Triantafyllos Chavakis
Integrins constitute a large group of adhesion receptors that are formed as heterodimers of α and β subunits. Their presence and activation status on the surface of leukocytes modulate a broad spectrum of processes in inflammation and immunity. This mini review critically outlines research advances with regard to the function of leukocyte integrins in regulating and integrating the onset and resolution of acute inflammation. Specifically, we summarize and discuss relevant, current literature that supports the multifunctional role of integrins and their partners...
March 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28286882/a-study-to-investigate-the-role-of-gulp-ced-6-gene-in-eat-me-signaling-in-cellular-efferocytosis-and-immunosurveillance
#16
H Banerjee, B Bazemore, A Barfield, D Crummity, C Krauss, G Payne, J Rousch, V Manglik
In this report, investigations were done to study human GULP/ CED 6 genes role in presenting cancer cells to scavenger cells. CED 6 SiRNA was used to knock out the gene in Astrocytoma (HTB-12) cell lines to study its effects on expression of various "eat me" signals on these cells including Phosphatidyl serine (PtdSer) expression, nitric oxide (NO) signaling and Leukotrine B4 (LTB4) expression and Caspase 3 activation. Investigations were done by fluorescence microscopy techniques, ELISA assay and colorimetric assays using a standard microplate reader and spectrophotometer...
December 2016: Immunological Disorders & Immunotherapy
https://www.readbyqxmd.com/read/28267881/distinctive-role-of-efferocytosis-in-dendritic-cell-maturation-and-migration-in-sterile-or-infectious-conditions
#17
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/28259375/sr-bi-a-multifunctional-receptor-in-cholesterol-homeostasis-and-atherosclerosis
#18
REVIEW
MacRae F Linton, Huan Tao, Edward F Linton, Patricia G Yancey
The HDL receptor scavenger receptor class B type I (SR-BI) plays crucial roles in cholesterol homeostasis, lipoprotein metabolism, and atherosclerosis. Hepatic SR-BI mediates reverse cholesterol transport (RCT) by the uptake of HDL cholesterol for routing to the bile. Through the selective uptake of HDL lipids, hepatic SR-BI modulates HDL composition and preserves HDL's atheroprotective functions of mediating cholesterol efflux and minimizing inflammation and oxidation. Macrophage and endothelial cell SR-BI inhibits the development of atherosclerosis by mediating cholesterol trafficking to minimize atherosclerotic lesion foam cell formation...
June 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28258690/tam-receptor-tyrosine-kinases-as-emerging-targets-of-innate-immune-checkpoint-blockade-for-cancer-therapy
#19
REVIEW
Yemsratch T Akalu, Carla V Rothlin, Sourav Ghosh
Cancer immunotherapy utilizing T-cell checkpoint inhibitors has shown tremendous clinical success. Yet, this mode of treatment is effective in only a subset of patients. Unresponsive patients tend to have non-T-cell-inflamed tumors that lack markers associated with the activation of adaptive anti-tumor immune responses. Notably, elimination of cancer cells by T cells is critically dependent on the optimal activity of innate immune cells. Therefore, identifying new targets that regulate innate immune cell function and promote the engagement of adaptive tumoricidal responses is likely to lead to the development of improved therapies against cancer...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28258107/nonantibiotic-macrolides-restore-airway-macrophage-phagocytic-function-with-potential-anti-inflammatory-effects-in-chronic-lung-diseases
#20
Sandra Hodge, Hai B Tran, Rhys Hamon, Eugene Roscioli, Greg Hodge, Hubertus Jersmann, Miranda Ween, Paul N Reynolds, Arthur Yeung, Jennifer Treiberg, Sibylle Wilbert
We reported defective efferocytosis associated with cigarette smoking and/or airway inflammation in chronic lung diseases, including chronic obstructive pulmonary disease, severe asthma, and childhood bronchiectasis. We also showed defects in phagocytosis of nontypeable Haemophilus influenzae (NTHi), a common colonizer of the lower airway in these diseases. These defects could be substantially overcome with low-dose azithromycin; however, chronic use may induce bacterial resistance. The aim of the present study was therefore to investigate two novel macrolides-2'-desoxy-9-(S)-erythromycylamine (GS-459755) and azithromycin-based 2'-desoxy molecule (GS-560660)-with significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and H...
May 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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