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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
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
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
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
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
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, with its associated bacteria, by neutrophils; bacteria are subsequently killed via neutrophil ROS...
September 28, 2016: European Journal of Immunology
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
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
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
Gargi S Sarode
No abstract text is available yet for this article.
May 2016: Journal of Oral and Maxillofacial Pathology: JOMFP
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
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
Hye-Won Yum, Hye-Kyung Na, Young-Joon Surh
The implication of inflammatory tissue damage in pathophysiology of human cancer as well as some metabolic disorders has been under intense investigation. Numerous studies have identified a series of critical signaling molecules involved in cellular responses to inflammatory stimuli. These include nuclear factor κB, peroxisome proliferator-activated receptor γ, nuclear factor erythroid 2 p45-related factor 2 and sterol regulatory element-binding protein 1. The proper regulation of these transcription factors mediating pro- and anti-inflammatory signaling hence provides an important strategy for the chemoprevention of inflammation-associated cancer...
October 2016: Seminars in Cancer Biology
Qiang Chen, Jie Chen, Jiong Chen, Xin-Jiang Lu
Liver X receptors (LXR) are modulators of metabolic processes and inflammation in mammals as nuclear receptors. However, the precise function of LXR in teleosts remains unclear. Here, we characterized a LXR gene (PaLXR) from ayu, Plecoglossus altivelis. The PaLXR transcript was expressed widely in all tissues studied, and changes in expression were observed in tissues and monocytes/macrophages (MO/MΦ) upon infection with the bacterium Edwardsiella ictaluri. PaLXR activation decreased the mRNA expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-10 upon E...
December 2016: Developmental and Comparative Immunology
Jill A Shults, Brenda J Curtis, Devin M Boe, Luis Ramirez, Elizabeth J Kovacs
In this study, the role and fate of AMs were examined in pulmonary inflammation after intoxication and injury. Clinical evidence has revealed that half of all burn patients brought to the emergency department are intoxicated at the time of injury. This combined insult results in amplified neutrophil accumulation and pulmonary edema, with an increased risk of lung failure and mortality, relative to either insult alone. We believe that this excessive pulmonary inflammation, which also parallels decreased lung function, is mediated in part by AMs...
August 16, 2016: Journal of Leukocyte Biology
Karina A Serban, Samin Rezania, Daniela N Petrusca, Christophe Poirier, Danting Cao, Matthew J Justice, Milan Patel, Irina Tsvetkova, Krzysztof Kamocki, Andrew Mikosz, Kelly S Schweitzer, Sean Jacobson, Angelo Cardoso, Nadia Carlesso, Walter C Hubbard, Katerina Kechris, Bogdan Dragnea, Evgeny V Berdyshev, Jeanette McClintock, Irina Petrache
Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism of release and function remain unknown. We assessed biochemical and functional characteristics of EMPs and circulating microparticles (cMPs) released by CS. CS exposure was sufficient to increase microparticle levels in plasma of humans and mice, and in supernatants of primary human lung microvascular endothelial cells. CS-released EMPs contained predominantly exosomes that were significantly enriched in let-7d, miR-191; miR-126; and miR125a, microRNAs that reciprocally decreased intracellular in CS-exposed endothelium...
2016: Scientific Reports
Talita Dacroce Tonin, Liliani Carolini Thiesen, Maria Luisa de Oliveira Nunes, Milena Fronza Broering, Marcos Paulo Donato, Marina Jagielski Goss, Marcel Petreanu, Rivaldo Niero, Isabel Daufenback Machado, José Roberto Santin
Here, we evaluate the anti-inflammatory and wound-healing effects of methanolic crude extract obtained from aerial parts (leaves and branches) of Rubus imperialis Chum. Schl. (Rosaceae) and the pure compound niga-ichigoside F1. Anti-inflammatory activity was determined in vivo and in vitro, and the healing effect was evaluated in surgical lesions in mice skin. The 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and H2O2-induced oxidative stress were used to determine antioxidant activity. The efferocytosis activity was also determined...
November 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Angélica T Vieira, Izabela Galvão, Laurence M Macia, Érica M Sernaglia, Marco Aurélio R Vinolo, Cristiana C Garcia, Luciana P Tavares, Flávio A Amaral, Lirlândia P Sousa, Flaviano S Martins, Charles R Mackay, Mauro M Teixeira
: Gout is a disease characterized by the deposition of monosodium urate (MSU) crystals in the joints. Continuous gout episodes may lead to unresolved inflammatory responses and tissue damage. We investigated the effects of a high-fiber diet and acetate, a short-chain fatty acid (SCFA) resulting from the metabolism of fiber by gut microbiota, on the inflammatory response in an experimental model of gout in mice. Injection of MSU crystals into the knee joint of mice induced neutrophil influx and inflammatory hypernociception...
August 5, 2016: Journal of Leukocyte Biology
Lisheng Jiang, Yingmin Chen, Xiaojing Huang, Ancai Yuan, Qin Shao, Jun Pu, Ben He
AIMS: Recent evidence indicates that the defective ability to clear apoptotic cells by macrophages (efferocytosis) and the resultant apoptotic cells accumulation in atherosclerotic plaques play an important role during the progression of unstable plaques. The cannabinoid type 2 receptor (CB2), has recently been emerging as a new target to reduce vulnerability and promote stability of plaques, however, the underlying mechanisms have not been studied in detail. In the present study, we investigated whether selective activation of CB2 improves efferocytosis of macrophages...
September 15, 2016: Life Sciences
Rohola Hosseini, Gerda E M Lamers, Hiwa M Soltani, Annemarie H Meijer, Herman P Spaink, Marcel J M Schaaf
Macrophages and neutrophils are the first responders to invading pathogens and contribute strongly to the host defense against intracellular pathogens. The collective interplay and dynamic interactions between these leukocytes are to a large extent not understood. In the present study, we have investigated their role using a combination of confocal laser-scanning and electron microscopy in a zebrafish model for tuberculosis, a local Mycobacterium marinum infection in the tissue of the larval tail fin. Our results show that neutrophils are efficient in phagocytosis of mycobacteria and that they contribute largely to their dissemination...
September 15, 2016: Journal of Cell Science
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