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https://www.readbyqxmd.com/read/29045901/by-capturing-inflammatory-lipids-released-from-dying-cells-the-receptor-cd14-induces-inflammasome-dependent-phagocyte-hyperactivation
#1
Ivan Zanoni, Yunhao Tan, Marco Di Gioia, James R Springstead, Jonathan C Kagan
A heterogeneous mixture of lipids called oxPAPC, derived from dying cells, can hyperactivate dendritic cells (DCs) but not macrophages. Hyperactive DCs are defined by their ability to release interleukin-1 (IL-1) while maintaining cell viability, endowing these cells with potent aptitude to stimulate adaptive immunity. Herein, we found that the bacterial lipopolysaccharide receptor CD14 captured extracellular oxPAPC and delivered these lipids into the cell to promote inflammasome-dependent DC hyperactivation...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29040215/role-of-receptor-for-advanced-glycation-end-products-in-regulating-lung-fluid-balance-in-lipopolysaccharide-induced-acute-lung-injury-and-infection-related-acute-respiratory-distress-syndrome
#2
Hao Wang, Tao Wang, Zhicheng Yuan, Yufang Cao, Yongfang Zhou, Junyun He, Yongchun Shen, Ni Zeng, Luqi Dai, Fuqiang Wen, Lei Chen
Receptor for advanced glycation end products (RAGE) is implicated in inflammatory responses in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), but its role in pulmonary edema formation remains unclear, especially in infection-related ARDS mainly caused by pneumonia or sepsis. In this study, we investigated the role of RAGE in alveolar fluid regulation by using RAGE gene knockout (RAGE) mice in a murine ALI model induced by lipopolysaccharide (LPS), and by comparing soluble RAGE (sRAGE) levels in serum and bronchial alveolar lavage fluid (BALF) between ARDS patients and control subjects...
October 16, 2017: Shock
https://www.readbyqxmd.com/read/29038465/nmi-and-ifp35-serve-as-proinflammatory-damps-during-cellular-infection-and-injury
#3
Zhikai Xiahou, Xiangli Wang, Juan Shen, Xiaoxiao Zhu, Feng Xu, Rong Hu, Deyin Guo, Henan Li, Yong Tian, Yingfang Liu, Huanhuan Liang
Damage-associated molecular patterns (DAMP) trigger innate immune response and exacerbate inflammation to combat infection and cellular damage. Identifying DAMPs and revealing their functions are thus of crucial importance. Here we report that two molecules, N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35) act as DAMPs and are released by activated macrophages during lipopolysaccharide-induced septic shock or acetaminophen-induced liver injury. We show that extracellular NMI and IFP35 activate macrophages to release proinflammatory cytokines by activating nuclear factor-κB through the Toll-like receptor 4 pathway...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29018138/endotoxin-preconditioning-reprograms-s1-tubules-and-macrophages-to-protect-the-kidney
#4
Takashi Hato, Amy Zollman, Zoya Plotkin, Tarek M El-Achkar, Bernhard F Maier, S Louise Pay, Shataakshi Dube, Pablo Cabral, Momoko Yoshimoto, Jeanette McClintick, Pierre C Dagher
Preconditioning with a low dose of endotoxin confers unparalleled protection against otherwise lethal models of sepsis. The mechanisms of preconditioning have been investigated extensively in isolated immune cells such as macrophages. However, the role of tissue in mediating the protective response generated by preconditioning remains unknown. Here, using the kidney as a model organ, we investigated cell type-specific responses to preconditioning. Compared with preadministration of vehicle, endotoxin preconditioning in the cecal ligation and puncture mouse model of sepsis led to significantly enhanced survival and reduced bacterial load in several organs...
October 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28993690/spred2-deficiecy-protects-mice-from-polymicrobial-septic-peritonitis-by-enhancing-inflammation-and-bacterial-clearance
#5
Junya Itakura, Miwa Sato, Toshihiro Ito, Megumi Mino, Soichiro Fushimi, Sakuma Takahashi, Teizo Yoshimura, Akihiro Matsukawa
Sepsis is an infection-induced systemic inflammatory syndrome and a major cause of death for critically ill patients. Here, we examined whether the absence of Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, influences host defense against polymicrobial sepsis (PMS) induced by cecal ligation and puncture (CLP). Compared to wild-type mice, Spred2(-/-) mice exhibited higher survival rates with increased level of leukocyte infiltration and local chemokine production and reduced plasma and peritoneal bacterial loads after CLP...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28991049/stearoyl-lysophosphatidylcholine-inhibits-endotoxin-induced-caspase-11-activation
#6
Wenbo Li, Wei Zhang, Meihong Deng, Patricia Loughran, Yiting Tang, Hong Liao, Xianying Zhang, Jian Liu, Timothy R Billiar, Ben Lu
Stearoyl lysophosphatidylcholine (LPC) exerts protective effect during endotoxemia and in experimental sepsis, but the underlying mechanism is unclear. Here, we demonstrated that stearoyl LPC could block caspase-11 mediated macrophage pyroptosis. In vitro, stearoyl LPC significantly decreased caspase-11 activation and pyroptosis induced by LPS plus CTB independent of the receptor G2A. Stearoyl LPC did not affect LPS uptake by mouse peritoneal macrophages but, did significantly inhibit the interaction between LPS and caspase-11...
October 4, 2017: Shock
https://www.readbyqxmd.com/read/28988116/macrophage-c-type-lectin-is-essential-for-phagosome-maturation-and-acidification-during-escherichia-coli-induced-peritonitis
#7
Wook-Bin Lee, Ji-Jing Yan, Ji-Seon Kang, Lark Kyun Kim, Young-Joon Kim
Sepsis is a life-threatening condition caused by an uncontrolled response to bacterial infection. Impaired bactericidal activity in the host is directly associated with severe sepsis; however, the underlying regulatory mechanism(s) is largely unknown. Here, we show that MCL (macrophage C-type lectin) plays a crucial role in killing bacteria during Escherichia coli-induced peritonitis. MCL-deficient mice with E. coli-induced sepsis showed lower survival rates and reduced bacterial clearance when compared with control mice, despite similar levels of proinflammatory cytokine production...
October 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28974614/inflammasome-activation-by-bacterial-outer-membrane-vesicles-requires-guanylate-binding-proteins
#8
Ryan Finethy, Sarah Luoma, Nichole Orench-Rivera, Eric M Feeley, Arun K Haldar, Masahiro Yamamoto, Thirumala-Devi Kanneganti, Meta J Kuehn, Jörn Coers
The Gram-negative bacterial cell wall component lipopolysaccharide (LPS) is recognized by the noncanonical inflammasome protein caspase-11 in the cytosol of infected host cells and thereby prompts an inflammatory immune response linked to sepsis. Host guanylate binding proteins (GBPs) promote infection-induced caspase-11 activation in tissue culture models, and yet their in vivo role in LPS-mediated sepsis has remained unexplored. LPS can be released from lysed bacteria as "free" LPS aggregates or actively secreted by live bacteria as a component of outer membrane vesicles (OMVs)...
October 3, 2017: MBio
https://www.readbyqxmd.com/read/28955505/necroptotic-debris-including-damaged-mitochondria-elicits-sepsis-like-syndrome-during-late-phase-tularemia
#9
Anju Singh, Sivakumar Periasamy, Meenakshi Malik, Chandra Shekhar Bakshi, Laurie Stephen, Jeffrey G Ault, Carmen A Mannella, Timothy J Sellati
Infection with Francisella tularensis ssp. tularensis (Ft) strain SchuS4 causes an often lethal disease known as tularemia in rodents, non-human primates, and humans. Ft subverts host cell death programs to facilitate their exponential replication within macrophages and other cell types during early respiratory infection (⩽72 h). The mechanism(s) by which cell death is triggered remains incompletely defined, as does the impact of Ft on mitochondria, the host cell's organellar 'canary in a coal mine'. Herein, we reveal that Ft infection of host cells, particularly macrophages and polymorphonuclear leukocytes, drives necroptosis via a receptor-interacting protein kinase 1/3-mediated mechanism...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28955042/acid-sphingomyelinase-inhibition-prevents-development-of-sepsis-sequelae-in-the-murine-liver
#10
Ha-Yeun Chung, C Julius Witt, Nayla Jbeily, Jorge Hurtado-Oliveros, Benjamin Giszas, Amelie Lupp, Markus H Gräler, Tony Bruns, Andreas Stallmach, Falk A Gonnert, Ralf A Claus
The molecular mechanisms of maladaptive response in liver tissue with respect to the acute and post-acute phase of sepsis are not yet fully understood. Long-term sepsis survivors might develop hepatocellular/hepatobiliary injury and fibrosis. Here, we demonstrate that acid sphingomyelinase, an important regulator of hepatocyte apoptosis and hepatic stellate cell (HSC) activation, is linked to the promotion of liver dysfunction in the acute phase of sepsis as well as to fibrogenesis in the long-term. In both phases, we observed a beneficial effect of partial genetic sphingomyelinase deficiency in heterozygous animals (smpd1(+/-)) on oxidative stress levels, hepatobiliary function, macrophage infiltration and on HSC activation...
September 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28953574/role-of-m2-macrophages-in-sepsis-induced-acute-kidney-injury
#11
Li Xing, Mu Genhua, Song Chunmei, Zhou Liangliang, He Lei, Jin Qin, Lu Zhongqian
BACKGROUND: Sepsis is a major cause of acute kidney injury (AKI), with high rates of morbidity and mortality. M2 macrophages have been shown to play important roles in the secretion of anti-inflammatory and tissue repair mediators. In this study, we investigate the role of M2 macrophages in sepsis-induced AKI by depleting these cells in vivo through the systemic administration of liposomal clodronate (LC). METHODS: Male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP) or sham surgery...
September 26, 2017: Shock
https://www.readbyqxmd.com/read/28947651/the-capsular-polysaccharide-of-acinetobacter-baumannii-is-an-obstacle-for-therapeutic-passive-immunization-strategies
#12
Shun Xin Wang-Lin, Ruth Olson, Janet M Beanan, Ulrike MacDonald, Joseph P Balthasar, Thomas A Russo
Acinetobacter baumannii has become an important concern to human health due to rapid development and wide spread of antimicrobial-resistant strains and high mortality associated with the infection. Passive immunizations with antisera targeting outer membrane proteins (OMPs) have shown encouraging results in protecting mice from A. baumannii infection; but monoclonal anti-OMP antibodies have not been developed and their potential therapeutic properties have not been explored. The goal of this report is to evaluate the antibacterial activity of monoclonal antibodies (mAbs) targeting outer membrane protein A (OmpA) of A...
September 25, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28947541/aging-impaired-filamentous-actin-polymerization-signaling-reduces-alveolar-macrophage-phagocytosis-of-bacteria
#13
Zhigang Li, Yang Jiao, Erica K Fan, Melanie J Scott, Yuehua Li, Song Li, Timothy R Billiar, Mark A Wilson, Xueyin Shi, Jie Fan
In elderly patients, bacterial infection often causes severe complications and sepsis. Compared to younger patients, older patients are more susceptible to sepsis caused by respiratory infection. Macrophage (Mϕ) phagocytosis of bacteria plays a critical role in the clearance of pathogens and the initiation of immune responses. It has been suggested that Mϕ exhibit age-related functional alterations, including reduced chemotaxis, phagocytosis, antibacterial defense, and the ability to generate reactive oxygen species...
September 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28941417/protective-role-of-liriodendrin-in-mice-with-dextran-sulphate-sodium-induced-ulcerative-colitis
#14
Zhen Zhang, Lei Yang, Botao Wang, Lanqiu Zhang, Qi Zhang, Dihua Li, Shukun Zhang, Hongwei Gao, Ximo Wang
Sargentodoxa cuneata, containing syringaresinol and its glycoside liriodendrin as the main bioactive compounds, is a well-known traditional Chinese medicine for treating intestinal inflammation. In our preliminary study, liriodendrin inhibited NF-kB activation in sepsis-induced acute lung injury. The present study was designed to investigate its effect on dextran sulfate sodium (DSS)-induced colitis in a mouse model and to explore the possible related mechanisms. Experimental colitis was established by giving mice drinking water containing 3% (w/v) DSS for 7days...
September 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28931916/salidroside-ameliorates-sepsis-induced-acute-lung-injury-and-mortality-via-downregulating-nf-%C3%AE%C2%BAb-and-hmgb1-pathways-through-the-upregulation-of-sirt1
#15
Kuo-Cheng Lan, Sung-Chuan Chao, Hsiao-Yi Wu, Chia-Lien Chiang, Ching-Chia Wang, Shing-Hwa Liu, Te-I Weng
Sepsis is a life-threatening medical condition. Salidroside, a substance isolated from Rhodiola rosea, possesses antioxidant and anti-inflammatory properties. The effect and mechanism of salidroside on sepsis-induced acute lung injury still remains to be well clarified. Here, we investigated the effect and mechanism of salidroside on septic mouse models and explored the role of salidroside-upregulated SIRT1. Salidroside inhibited the inflammatory responses and HMGB1 productions in bacterial lipopolysaccharide (LPS)-treated macrophages and mice...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931235/monoclonal-antibody-protects-against-acinetobacter-baumannii-infection-by-enhancing-bacterial-clearance-and-evading-sepsis
#16
Travis B Nielsen, Paul Pantapalangkoor, Brian M Luna, Kevin W Bruhn, Jun Yan, Ken Dekitani, Sarah Hsieh, Brandon Yeshoua, Bryan Pascual, Evgeny Vinogradov, Kristine M Hujer, T Nicholas Domitrovic, Robert A Bonomo, Thomas A Russo, Magda Lesczcyniecka, Thomas Schneider, Brad Spellberg
Background: Extremely drug-resistant (XDR) Acinetobacter baumannii is one of the most commonly encountered, highly resistant pathogens requiring novel therapeutic interventions. Methods: We developed C8, a monoclonal antibody (mAb), by immunizing mice with sublethal inocula of a hypervirulent XDR clinical isolate. Results: C8 targets capsular carbohydrate on the bacterial surface, enhancing opsonophagocytosis. Treating with a single dose of C8 as low as 0...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28930915/microvesicle-subsets-in-sepsis-due-to-community-acquired-pneumonia-compared-to-faecal-peritonitis
#17
Hazem M S Lashin, Suchita Nadkarni, Silvia Oggero, Hefin R Jones, Julian C Knight, Charles J Hinds, Mauro Perretti
RATIONALE: Microvesicles (MV) act as a non-soluble means of inter-cellular communication, with effector roles in disease pathogenesis and potentially as biomarkers. Previously, we reported that neutrophil MV expressing alpha-2-macroglobulin (A2MG) are protective in experimental sepsis and associate with survival in a small cohort of patients with sepsis due to community acquired pneumonia (CAP). OBJECTIVES: To characterise MV profiles in sepsis due to CAP or faecal peritonitis (FP) and determine their relation to outcome...
September 19, 2017: Shock
https://www.readbyqxmd.com/read/28929026/curcumin-longa-extract-loaded-nanoemulsion-improves-the-survival-of-endotoxemic-mice-by-inhibiting-nitric-oxide-dependent-hmgb1-release
#18
Min Young Ahn, Jung Seok Hwang, Su Bi Lee, Sun Ah Ham, Jinwoo Hur, Jun Tae Kim, Han Geuk Seo
BACKGROUND: High mobility group box 1 (HMGB1) is a well-known damage-related alarmin that participates in cellular inflammatory responses. However, the mechanisms leading to HMGB1 release in inflammatory conditions and the therapeutic agents that could prevent it remain poorly understood. This study attempted to examine whether the Curcumin longa herb, which is known to have anti-inflammatory property, can modulate cellular inflammatory responses by regulating HMGB1 release. METHODS: The murine macrophage RAW264...
2017: PeerJ
https://www.readbyqxmd.com/read/28918906/radiotherapy-and-the-tumor-microenvironment-the-macro-picture
#19
EDITORIAL
Emma Louise Walton
In this issue of the Biomedical Journal, we explore the inner workings of tumor-associated macrophages and seek to understand how these cells can boost or limit the efficacy of radiotherapy, depending on the context. We also highlight a study revealing that staffing patterns in the intensive care unit may affect the outcome of patients with severe sepsis. Finally, we learn how an advanced imaging technique can improve endodontic treatment planning.
August 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28918754/macrophage-activation-like-syndrome-an-immunological-entity-associated-with-rapid-progression-to-death-in-sepsis
#20
Evdoxia Kyriazopoulou, Konstantinos Leventogiannis, Anna Norrby-Teglund, Georgios Dimopoulos, Aikaterini Pantazi, Stylianos E Orfanos, Nikoletta Rovina, Iraklis Tsangaris, Theologia Gkavogianni, Elektra Botsa, Eleftheria Chassiou, Anastasia Kotanidou, Christina Kontouli, Panagiotis Chaloulis, Dimitrios Velissaris, Athina Savva, Jonas-Sundén Cullberg, Karolina Akinosoglou, Charalambos Gogos, Apostolos Armaganidis, Evangelos J Giamarellos-Bourboulis
BACKGROUND: A subanalysis of a randomized clinical trial indicated sepsis survival benefit from interleukin (IL)-1 blockade in patients with features of the macrophage activation-like syndrome (MALS). This study aimed to investigate the frequency of MALS and to develop a biomarker of diagnosis and prognosis. METHODS: Patients with infections and systemic inflammatory response syndrome were assigned to one test cohort (n = 3417) and a validation cohort (n = 1704)...
September 18, 2017: BMC Medicine
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