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Efferocytosis

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https://www.readbyqxmd.com/read/27895181/complement-protein-c1q-enhances-macrophage-foam-cell-survival-and-efferocytosis
#1
Marc C Pulanco, Jason Cosman, Minh-Minh Ho, Jessica Huynh, Karina Fing, Jacqueline Turcu, Deborah A Fraser
In the atherosclerotic lesion, macrophages ingest high levels of damaged modified low-density lipoproteins (LDLs), generating macrophage foam cells. Foam cells undergo apoptosis and, if not efficiently cleared by efferocytosis, can undergo secondary necrosis, leading to plaque instability and rupture. As a component of the innate immune complement cascade, C1q recognizes and opsonizes modified forms of LDL, such as oxidized or acetylated LDL, and promotes ingestion by macrophages in vitro. C1q was shown to be protective in an atherosclerosis model in vivo...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27881672/mineralocorticoid-receptor-deficiency-in-macrophages-inhibits-atherosclerosis-by-affecting-foam-cell-formation-and-efferocytosis
#2
Zhu-Xia Shen, Xiao-Qing Chen, Xue-Nan Sun, Jian-Yong Sun, Wu-Chang Zhang, Xiao-Jun Zheng, Yu-Yao Zhang, Huan-Jing Shi, Jia-Wei Zhang, Chao Li, Jun Wang, Xu Liu, Sheng-Zhong Duan
Mineralocorticoid receptor (MR) has been considered as a potential target for treating atherosclerosis. However, the cellular and molecular mechanisms are not completely understood. We aim to explore the functions and mechanisms of macrophage MR in atherosclerosis. Atherosclerosis-susceptible LDLRKO chimeric mice with bone marrow cells from floxed control (FC) mice or from myeloid MR knockout (MRKO) mice were generated and fed with high cholesterol diet. Oil red O staining showed that MRKO decreased atherosclerotic lesion area in LDLRKO mice...
November 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27868302/reduced-dna-methylation-of-sphingosine-1-phosphate-receptor-5-in-alveolar-macrophages-in-copd-a-potential-link-to-failed-efferocytosis
#3
Jameel Barnawi, Hubertus Jersmann, Rainer Haberberger, Sandra Hodge, Robyn Meech
BACKGROUND AND OBJECTIVE: We previously showed that alveolar macrophages from COPD patients are defective in their ability to phagocytose apoptotic cells ('efferocytosis') and that this defect is potentially linked to the sphingosine-1 phosphate (S1P) system, in particular the sphingosine-1 phosphate receptor 5 (S1PR5). In alveolar macrophages from COPD patients, S1PR5 mRNA expression levels increased and were correlated with both lung function and efferocytosis. However, it us unknown whether these changes are under epigenetic control via DNA methylation or whether DNA methylation directly modulates macrophage function...
November 20, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27853832/old-drugs-with-new-skills-fenoprofen-as-an-allosteric-enhancer-at-melanocortin-receptor-3
#4
Trinidad Montero-Melendez, Rachel A E Forfar, Jennifer M Cook, Jeffrey C Jerman, Debra L Taylor, Mauro Perretti
The efficiency of drug research and development has paradoxically declined over the last decades despite major scientific and technological advances, promoting new cost-effective strategies such as drug repositioning by systematic screening for new actions of known drugs. Here, we performed a screening for positive allosteric modulators (PAMs) at melanocortin (MC) receptors. The non-steroidal anti-inflammatory drug fenoprofen, but not the similar compound ibuprofen, presented PAM activity at MC3, MC4, and MC5 receptors...
November 16, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27834816/targeting-the-tam-receptors-in-leukemia
#5
REVIEW
Madeline G Huey, Katherine A Minson, H Shelton Earp, Deborah DeRyckere, Douglas K Graham
Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma...
November 8, 2016: Cancers
https://www.readbyqxmd.com/read/27827458/microrna-126-overexpression-rescues-diabetes-induced-impairment-in-efferocytosis-of-apoptotic-cardiomyocytes
#6
Sahana Suresh Babu, Rajarajan A Thandavarayan, Darukeshwara Joladarashi, Prince Jeyabal, Shashirekha Krishnamurthy, Arvind Bhimaraj, Keith A Youker, Prasanna Krishnamurthy
Efferocytosis, a process of clearance of apoptotic cells by phagocytes, is essential for successful resolution of inflammation and maintenance of tissue homeostasis. Diabetes compromises the function of macrophages leading to adverse inflammatory response during wound healing, myocardial injury, atherosclerosis and autoimmune disorders. However, the effect of diabetes on macrophage-mediated efferocytosis of apoptotic cardiomyocytes (ACM) and the molecular mechanisms involved are not understood so far. In the present study we found that invitro efferocytosis of ACM was impaired in macrophages from db/db (diabetic) mice...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27815871/quantitative-efferocytosis-assays
#7
Amanda L Evans, Jack W D Blackburn, Charles Yin, Bryan Heit
Efferocytosis, the phagocytic removal of apoptotic cells, is a dynamic process requiring recruitment of numerous regulatory proteins to forming efferosomes in a tightly regulated manner. Herein we describe microscopy-based methods for the enumeration of efferocytic events and characterization of the spatiotemporal dynamics of signaling molecule recruitment to efferosomes, using genetically encoded probes and immunofluorescent labeling. While these methods are illustrated using macrophages, they are applicable to any efferocytic cell type...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27802331/inflammation-in-sickle-cell-disease-differential-and-down-expressed-plasma-levels-of-annexin-a1-protein
#8
Lidiane S Torres, Jéssika V Okumura, Danilo G H Silva, Kallyne K O Mimura, Édis Belini-Júnior, Renan G Oliveira, Clarisse L C Lobo, Sonia M Oliani, Claudia R Bonini-Domingos
Sickle cell disease (SCD) is an inherited hemolytic anemia whose pathophysiology is driven by polymerization of the hemoglobin S (Hb S), leading to hemolysis and vaso-occlusive events. Inflammation is a fundamental component in these processes and a continuous inflammatory stimulus can lead to tissue damages. Thus, pro-resolving pathways emerge in order to restore the homeostasis. For example there is the annexin A1 (ANXA1), an endogenous anti-inflammatory protein involved in reducing neutrophil-endothelial interactions, accelerating neutrophil apoptosis and stimulating macrophage efferocytosis...
2016: PloS One
https://www.readbyqxmd.com/read/27739519/s-aureus-blocks-efferocytosis-of-neutrophils-by-macrophages-through-the-activity-of-its-virulence-factor-alpha-toxin
#9
Taylor S Cohen, Omari Jones-Nelson, Meghan Hotz, Lily Cheng, Lloyd S Miller, JoAnn Suzich, C Kendall Stover, Bret R Sellman
Bacterial pneumonia, such as those caused by Staphylococcus aureus, is associated with an influx of inflammatory neutrophils into the lung tissue and airways. Regulation and clearance of recruited neutrophils is essential for preventing tissue damage by "friendly fire", a responsibility of macrophages in a process called efferocytosis. We hypothesized that S. aureus impairs efferocytosis by alveolar macrophages (AMs) through the activity of the secreted virulence factor alpha toxin (AT), which has been implicated in altering the antimicrobial function of AMs...
October 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27733579/galectin-3-null-mice-display-defective-neutrophil-clearance-during-acute-inflammation
#10
Rachael D Wright, Patricia R Souza, Magdalena B Flak, Prasheetha Thedchanamoorthy, Lucy V Norling, Dianne Cooper
Galectin-3 has been associated with a plethora of proinflammatory functions because of its ability, among others, to promote neutrophil activation and because of the reduction in neutrophil recruitment in models of infection in Gal-3-null mice. Conversely, it has also been linked to resolution of inflammation through its actions as an opsonin and its ability to promote efferocytosis of apoptotic neutrophils. Using a self-resolving model of peritonitis, we have addressed the modulation and role of Gal-3 in acute inflammation...
October 12, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27725526/macrophage-apoptosis-and-efferocytosis-in-the-pathogenesis-of-atherosclerosis
#11
MacRae F Linton, Vladimir R Babaev, Jiansheng Huang, Edward F Linton, Huan Tao, Patricia G Yancey
Macrophage apoptosis and the ability of macrophages to clean up dead cells, a process called efferocytosis, are crucial determinants of atherosclerosis lesion progression and plaque stability. Environmental stressors initiate endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR). Unresolved ER stress with activation of the UPR initiates apoptosis. Macrophages are resistant to apoptotic stimuli, because of activity of the PI3K/Akt pathway. Macrophages express 3 Akt isoforms, Akt1, Akt2 and Akt3, which are products of distinct but homologous genes...
October 8, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27707882/ifn-%C3%AE-targets-macrophage-mediated-immune-responses-toward-staphylococcus-aureus
#12
Mallary C Greenlee-Wacker, William M Nauseef
Infections, especially with Staphylococcus aureus (SA), commonly cause morbidity and mortality in patients with chronic granulomatous disease (CGD), a condition characterized by a defective phagocyte oxidase. IFN-γ reduces the frequency and consequences of infection in CGD by mechanisms that remain unknown. As IFN-γ promotes bacterial killing, efferocytosis of effete polymorphonuclear neutrophils (PMN), and cytokine production in macrophages-the same macrophage effector functions that are impaired in response to SA-we hypothesized that IFN-γ may reverse these defects and thereby, augment macrophage control of SA during infection...
October 5, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27689709/the-effect-of-colonization-with-potentially-pathogenic-microorganisms-on-efferocytosis-in-chronic-obstructive-pulmonary-disease
#13
Sandra Hodge, Hubertus Jersmann, Paul N Reynolds
No abstract text is available yet for this article.
October 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27682622/il-1%C3%AE-il-18-and-eicosanoids-promote-neutrophil-recruitment-to-pore-induced-intracellular-traps-following-pyroptosis
#14
Ine Jorgensen, Joseph P Lopez, Stefan A Laufer, Edward A Miao
Inflammasomes activate caspase-1, initiating a lytic form of programmed cell death termed pyroptosis, which is an important innate immune defense mechanism against intracellular infections. We recently demonstrated in a mouse infection model of pyroptosis that instead of releasing bacteria into the extracellular space, bacteria remain trapped within the pyroptotic cell corpse, termed the pore-induced intracellular trap (PIT). This trapping mediates efferocytosis of the PIT and associated bacteria by neutrophils; bacteria are subsequently killed via neutrophil ROS...
December 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27680884/differential-effects-of-p38-mapk-pi3k-or-rho-kinase-inhibitors-on-bacterial-phagocytosis-and-efferocytosis-by-macrophages-in-copd
#15
Martin A Bewley, Kylie B R Belchamber, Kirandeep K Chana, Richard C Budd, Gavin Donaldson, Jadwiga A Wedzicha, Christopher E Brightling, Iain Kilty, Louise E Donnelly, Peter J Barnes, Dave Singh, Moira K B Whyte, David H Dockrell
Pulmonary inflammation and bacterial colonization are central to the pathogenesis of chronic obstructive pulmonary disease (COPD). Defects in macrophage phagocytosis of both bacteria and apoptotic cells contribute to the COPD phenotype. Small molecule inhibitors with anti-inflammatory activity against p38 mitogen activated protein kinases (MAPKs), phosphatidyl-inositol-3 kinase (PI3K) and Rho kinase (ROCK) are being investigated as novel therapeutics in COPD. Concerns exist, however, about off-target effects...
2016: PloS One
https://www.readbyqxmd.com/read/27659679/an-imbalance-between-specialized-pro-resolving-lipid-mediators-and-pro-inflammatory-leukotrienes-promotes-instability-of-atherosclerotic-plaques
#16
Gabrielle Fredman, Jason Hellmann, Jonathan D Proto, George Kuriakose, Romain A Colas, Bernhard Dorweiler, E Sander Connolly, Robert Solomon, David M Jones, Eric J Heyer, Matthew Spite, Ira Tabas
Chronic unresolved inflammation plays a causal role in the development of advanced atherosclerosis, but the mechanisms that prevent resolution in atherosclerosis remain unclear. Here, we use targeted mass spectrometry to identify specialized pro-resolving lipid mediators (SPM) in histologically-defined stable and vulnerable regions of human carotid atherosclerotic plaques. The levels of SPMs, particularly resolvin D1 (RvD1), and the ratio of SPMs to pro-inflammatory leukotriene B4 (LTB4), are significantly decreased in the vulnerable regions...
September 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/27648302/proteolytic-inactivation-of-nuclear-alarmin-high-mobility-group-box-1-by-complement-protease-c1s-during-apoptosis
#17
J G Yeo, J Leong, T Arkachaisri, Y Cai, B H D Teo, J H T Tan, L Das, J Lu
Effective clearance of apoptotic cells by phagocytes prevents the release of intracellular alarmins and manifestation of autoimmunity. This prompt efferocytosis is complemented by intracellular proteolytic degradation that occurs within the apoptotic cells and in the efferosome of the phagocytes. Although the role of extracellular proteases in apoptotic cells clearance is unknown, the strong association of congenital C1s deficiency with Systemic Lupus Erythematosus highlights the protective nature that this extracellular protease has against autoimmunity...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27601803/efferocytosis-in-oral-squamous-cell-carcinoma
#18
Gargi S Sarode
No abstract text is available yet for this article.
May 2016: Journal of Oral and Maxillofacial Pathology: JOMFP
https://www.readbyqxmd.com/read/27573815/pyroptosis-triggers-pore-induced-intracellular-traps-pits-that-capture-bacteria-and-lead-to-their-clearance-by-efferocytosis
#19
Ine Jorgensen, Yue Zhang, Bryan A Krantz, Edward A Miao
Inflammasomes activate caspase-1 in response to cytosolic contamination or perturbation. This inflammatory caspase triggers the opening of the GSDMD pore in the plasma membrane, resulting in lytic cell death called pyroptosis. We had previously assumed that pyroptosis releases intracellular bacteria to the extracellular space. Here, we find that viable bacteria instead remain trapped within the cellular debris of pyroptotic macrophages. This trapping appears to be an inevitable consequence of how osmotic lysis ruptures the plasma membrane, and may also apply to necroptosis and some forms of nonprogrammed necrosis...
September 19, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27558346/clearance-of-apoptotic-neutrophils-and-resolution-of-inflammation
#20
REVIEW
Mallary C Greenlee-Wacker
The engulfment of apoptotic cells by phagocytes, a process referred to as efferocytosis, is essential for maintenance of normal tissue homeostasis and a prerequisite for the resolution of inflammation. Neutrophils are the predominant circulating white blood cell in humans, and contain an arsenal of toxic substances that kill and degrade microbes. Neutrophils are short-lived and spontaneously die by apoptosis. This review will highlight how the engulfment of apoptotic neutrophils by human phagocytes occurs, how heterogeneity of phagocyte populations influences efferocytosis signaling, and downstream consequences of efferocytosis...
September 2016: Immunological Reviews
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