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Efferocytosis

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https://www.readbyqxmd.com/read/28428217/microrna-33-regulates-macrophage-autophagy-in-atherosclerosis
#1
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
#2
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/28407017/characterizing-the-anti-inflammatory-and-tissue-protective-actions-of-a-novel-annexin-a1-peptide
#3
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%A2-sup-12-14-sup-prostaglandin-j-sub-2-sub-exerts-pro-resolving-effects-through-nrf2-induced-expression-of-cd36-and-heme-oxygenase-1
#4
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/28376111/coordinated-balance-of-rac1-and-rhoa-plays-key-roles-in-determining-phagocytic-appetite
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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...
March 1, 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
#13
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/non-antibiotic-macrolides-restore-airway-macrophage-phagocytic-function-with-potential-anti-inflammatory-effects-in-chronic-lung-diseases
#14
Sandra J Hodge, Hai 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 COPD, severe asthma and childhood bronchiectasis. We also showed defects in phagocytosis of non-typeable H. influenzae (NTHi), a common colonizer of the lower airway in these diseases. These defects could be substantially overcome with low-dose Azithromycin; however, chronic usage may induce bacterial resistance. We investigated two novel macrolides, GS-459755 (2'-desoxy-9-(S)-erythromycylamine) and GS-560660 (Azithromycin-based 2'-desoxy molecule) with significantly diminished antibiotic activity against S...
March 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28247013/latest-perspectives-on-macrophages-in-bone-homeostasis
#15
REVIEW
Aline Bozec, Didier Soulat
Knowledge about macrophages residing in the bone, also known as osteal macrophages or osteomacs, is still limited. A hallmark of this peculiar myeloid population is the expression of macrophage markers distinct from the markers found on osteoclast surface. In bone, osteomacs are in contact with osteoblasts, where they are involved in regulating bone homeostasis. However, additional macrophage subtypes already present in the bone marrow or recruited from the blood circulation could have further functions, which could be all important for the maintenance of the bone architecture and its associated functions...
February 28, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28194400/eating-the-dead-to-keep-atherosclerosis-at-bay
#16
REVIEW
Megan L Brophy, Yunzhou Dong, Hao Wu, H N Ashiqur Rahman, Kai Song, Hong Chen
Atherosclerosis is the primary cause of coronary heart disease (CHD), ischemic stroke, and peripheral arterial disease. Despite effective lipid-lowering therapies and prevention programs, atherosclerosis is still the leading cause of mortality in the United States. Moreover, the prevalence of CHD in developing countries worldwide is rapidly increasing at a rate expected to overtake those of cancer and diabetes. Prominent risk factors include the hardening of arteries and high levels of cholesterol, which lead to the initiation and progression of atherosclerosis...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28185913/macrophages-and-skeletal-health
#17
REVIEW
Megan N Michalski, Laurie K McCauley
Bone is in a constant state of remodeling, a process which was once attributed solely to osteoblasts and osteoclasts. Decades of research has identified many other populations of cells in the bone that participate and mediate skeletal homeostasis. Recently, osteal macrophages emerged as vital participants in skeletal remodeling and osseous repair. The exact mechanistic roles of these tissue-resident macrophages are currently under investigation. Macrophages are highly plastic in response to their micro-environment and are typically classified as being pro- or anti-inflammatory (pro-resolving) in nature...
February 7, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28184013/phosphatidylserine-sensing-by-tam-receptors-regulates-akt-dependent-chemoresistance-and-pd-l1-expression
#18
Canan Kasikara, Sushil Kumar, Stanley Kimani, Wen-I Tsou, Ke Geng, Viralkumar Davra, Ganapathy Sriram, Connor Devoe, Khanh-Quynh Nguyen, Anita Antes, Allen Krantz, Grzegorz Rymarczyk, Andrzej Wilczynski, Cyril Empig, Bruce D Freimark, Michael Gray, Kyle Schlunegger, Jeff Hutchins, Sergei V Kotenko, Raymond B Birge
Tyro3, Axl and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases (RTKs) that bind vitamin K-dependent endogenous ligands, Protein S (ProS) and Growth arrest specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radio-resistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment (TME) that can suppress host anti-tumor immunity...
February 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28169339/dna-methylation-governs-the-dynamic-regulation-of-inflammation-by-apoptotic-cells-during-efferocytosis
#19
Clare A Notley, Christine K Jordan, Jenny L McGovern, Mark A Brown, Michael R Ehrenstein
Efficient clearance of apoptotic cells (AC) is pivotal in preventing autoimmunity and is a potent immunosuppressive stimulus. However, activation of cells prior to apoptosis abolishes their immunoregulatory properties. Here we show using the antigen-induced model of arthritis that the degree of DNA methylation within AC confers their immunomodulatory plasticity. DNA isolated from resting and activated AC mimicked their respective immune effects. Demethylation of DNA abrogated the protective effect of AC whereas remethylation of AC DNA reversed the effects of activation and restored the ability to inhibit inflammation...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167649/efferocytosis-signaling-in-the-regulation-of-macrophage-inflammatory-responses
#20
REVIEW
Michael R Elliott, Kyle M Koster, Patrick S Murphy
Since the pioneering work of Elie Metchnikoff and the discovery of cellular immunity, the phagocytic clearance of cellular debris has been considered an integral component of resolving inflammation and restoring function of damaged and infected tissues. We now know that the phagocytic clearance of dying cells (efferocytosis), particularly by macrophages and other immune phagocytes, has profound consequences on innate and adaptive immune responses in inflamed tissues. These immunomodulatory effects result from an array of molecular signaling events between macrophages, dying cells, and other tissue-resident cells...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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