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Phagocytic activity of neutrophils

Rugmani Padmanabhan Iyer, Lisandra E de Castro Brás, Nicolle L Patterson, Manishabrata Bhowmick, Elizabeth R Flynn, Majdouline Asher, Presley L Cannon, Kristine Y Deleon-Pennell, Gregg B Fields, Merry L Lindsey
Matrix metalloproteinase-9 (MMP-9) is robustly elevated in the first week post-myocardial infarction (MI). Targeted deletion of the MMP-9 gene attenuates cardiac remodeling post-MI by reducing macrophage infiltration and collagen accumulation through increased apoptosis and reduced inflammation. In this study, we used a translational experimental design to determine whether selective MMP-9 inhibition early post-MI would be an effective therapeutic strategy in mice. We enrolled male C57BL/6J mice (3-6months old, n=116) for this study...
October 13, 2016: Journal of Molecular and Cellular Cardiology
Ding-Jun Hao, Cuicui Liu, Lingling Zhang, Bo Chen, Qian Zhang, Rui Zhang, Jing An, Jingjing Zhao, Mingmei Wu, Yi Wang, Alfred Simental, Baorong He, Hao Yang
The gradual deterioration following central nervous system (CNS) injuries or neurodegenerative disorders is usually accompanied by infiltration of degenerated and apoptotic neural tissue debris. A rapid and efficient clearance of these deteriorated cell products is of pivotal importance in creating a permissive environment for regeneration of those damaged neurons. Our recent report revealed that the phagocytic activity of olfactory ensheathing cells (OECs) can make a substantial contribution to neuronal growth in such a hostile environment...
October 14, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Adam P Levine, Anthony W Segal
This review is devoted to a consideration of the way in which the NADPH oxidase of neutrophils, NOX2, functions to enable the efficient killing of bacteria and fungi. It includes a critical examination of the current dogma that its primary purpose is the generation of hydrogen peroxide as substrate for myeloperoxidase-catalyzed generation of hypochlorite. Instead, it is demonstrated that NADPH oxidase functions to optimize the ionic and pH conditions within the vacuole for the solubilization and optimal activity of the proteins released into this compartment from the cytoplasmic granules, which kill and digest the microbes...
August 2016: Microbiology Spectrum
E Yu Sherstoboev, O G Shitikova, N V Masnaya, M G Danilets, E S Trofimova, A A Ligacheva, P G Madonov, D N Kinsht, K I Ershov, M A Shilova
Course treatment with IFN-α2b immobilized on polyethylene glycol stimulates phagocytic activity of peritoneal macrophages and neutrophils, enhances humoral immune response in CBA/CaLac mice, stimulates IL-4 synthesis, and suppresses IFN-γ production by mitogenstimulated splenocytes from experimental animals.
September 2016: Bulletin of Experimental Biology and Medicine
Suelen Martins Perobelli, Ana Carolina Terra Mercadante, Rômulo Gonçalves Galvani, Triciana Gonçalves-Silva, Ana Paula Gregório Alves, Antonio Pereira-Neves, Marlene Benchimol, Alberto Nóbrega, Adriana Bonomo
Acute graft-versus-host disease (aGVHD) is the main complication of allogeneic hematopoietic stem cell transplantation, and many efforts have been made to overcome this important limitation. We showed previously that G-CSF treatment generates low-density splenic granulocytes that inhibit experimental aGVHD. In this article, we show that aGVHD protection relies on incoming IL-10(+) neutrophils from G-CSF-treated donor spleen (G-Neutrophils). These G-Neutrophils have high phagocytic capacity, high peroxide production, low myeloperoxidase activity, and low cytoplasmic granule content, which accounts for their low density...
October 5, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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
Aurélie Gabrion, Isabelle Hmitou, Despina Moshous, Bénédicte Neven, Alain Lefèvre-Utile, Jean-Sébastien Diana, Félipe Suarez, Capucine Picard, Stéphane Blanche, Alain Fischer, Marina Cavazzana, Fabien Touzot
BACKGROUND: Chronic granulomatous disease (CGD) is primary immunodeficiency caused by defective production of reactive oxygen species in phagocytic cells that results in life-threatening infections and severe inflammatory manifestations. The treatment of inflammatory manifestations remains challenging, as it can be associated with an increased risk of infections. Previous studies have shown that CGD phagocytes display a defect in autophagy and a reactive oxygen species-independent activation of the inflammasome...
October 1, 2016: Journal of Allergy and Clinical Immunology
Kenta Fujimoto, Takehiro Motowaki, Naoya Tamura, Yasuaki Aratani
Myeloperoxidase (MPO), a major component of neutrophils, catalyzes the production of hypochlorous acid from hydrogen peroxide and chloride anion. Phagocytosis is a critical event induced by neutrophils for host defense and inflammation. Interestingly, we found that MPO-deficient (MPO(-/-)) neutrophils engulfed larger amounts of zymosan than wild-type neutrophils. Blocking of the CD11b subunit of complement receptor 3 (CR3) as well as inhibition of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) dramatically reduced zymosan phagocytosis...
October 4, 2016: Free Radical Research
Lílian Cataldi Rodrigues, Adriana Secatto, Carlos A Sorgi, Naiara N Dejani, Alexandra I Medeiros, Morgana Kelly Borges Prado, Simone Gusmão Ramos, Richard D Cummings, Sean R Stowell, Lúcia Helena Faccioli, Marcelo Dias-Baruffi
Histoplasma capsulatum is a dimorphic fungus that develops a yeast-like morphology in host's tissue, responsible for the pulmonary disease histoplasmosis. The recent increase in the incidence of histoplasmosis in immunocompromised patients highlights the need of understanding immunological controls of fungal infections. Here, we describe our discovery of the role of endogenous galectin-1 (Gal-1) in the immune pathophysiology of experimental histoplasmosis. All infected wild-type (WT) mice survived while only 1/3 of Lgals1(-/-) mice genetically deficient in Gal-1 survived 30 days after infection...
2016: Mediators of Inflammation
Sandra Lemesch, Werner Ribitsch, Gernot Schilcher, Walter Spindelböck, Hildegard Hafner-Gießauf, Gunther Marsche, Lisa Pasterk, Doris Payerl, Bianca Schmerböck, Monika Tawdrous, Alexander R Rosenkranz, Philipp Stiegler, Gerd Kager, Seth Hallström, Karl Oettl, Katharina Eberhard, Angela Horvath, Bettina Leber, Vanessa Stadlbauer
Bacterial infection and sepsis are common complications of chronic kidney disease (CKD). A vicious cycle of increased gut permeability, endotoxemia, inadequate activation of the innate immune system and resulting innate immune dysfunction is hypothesized. We assessed endotoxemia, neutrophil function and its relation to oxidative stress, inflammation and gut permeability in patients with CKD grade 3-5 without renal replacement therapy (CKD group, n = 57), patients with CKD stage 5 undergoing haemodialysis (HD, n = 32) or peritoneal dialysis (PD, n = 28) and patients after kidney transplantation (KT, n = 67) in a cross-sectional observational study...
October 4, 2016: Scientific Reports
Man Li, Yong He, Zhou Zhou, Teresa Ramirez, Yueqiu Gao, Yanhang Gao, Ruth A Ross, Haixia Cao, Yan Cai, Mingjiang Xu, Dechun Feng, Ping Zhang, Suthat Liangpunsakul, Bin Gao
OBJECTIVES: Chronic-plus-binge ethanol feeding activates neutrophils and exacerbates liver injury in mice. This study investigates how recent excessive drinking affects peripheral neutrophils and liver injury in alcoholics, and how miR-223, one of the most abundant microRNAs (miRNAs) in neutrophils, modulates neutrophil function and liver injury in ethanol-fed mice. DESIGNS: Three hundred alcoholics with (n=140) or without (n=160) recent excessive drinking and 45 healthy controls were enrolled...
September 27, 2016: Gut
Akinobu Kamei, Geli Gao, Geoffrey Neale, Lip Nam Loh, Peter Vogel, Paul G Thomas, Elaine I Tuomanen, Peter J Murray
Infection is the single greatest threat to survival during cancer chemotherapy because of depletion of bone marrow-derived immune cells. Phagocytes, especially neutrophils, are key effectors in immunity to extracellular pathogens, which has limited the development of new approaches to protect patients with cancer and chemotherapy-induced neutropenia. Using a model of vaccine-induced protection against lethal Pseudomonas aeruginosa pneumonia in the setting of chemotherapy-induced neutropenia, we found a population of resident lung macrophages in the immunized lung that mediated protection in the absence of neutrophils, bone marrow-derived monocytes, or antibodies...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Taj Ali Khan, Kalsoom Kalsoom, Asif Iqbal, Huma Asif, Hazir Rahman, Syed Omar Farooq, Hassan Naveed, Umar Nasir, Muhammad Usman Amin, Mubashir Hussain, Hamid Nawaz Tipu, Andrei Florea
Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the five structural genes (CYBB, CYBA, NCF1, NCF2, and NCF4) that typically results in a decrease in function or inability to generate a respiratory burst, leading to defective killing of pathogens, including fungi and intracellular bacteria. Mutations in CYBB, encoding the gp91phox (also known as NOX2) result in X-linked CGD account for approximately 65% of CGD cases. Here, we aimed the characterization of a novel missense mutation c...
September 23, 2016: Microbial Pathogenesis
Cortney L Armstrong, Irina Miralda, Adam C Neff, Shifu Tian, Aruna Vashishta, Lisandra Perez, Junyi Le, Richard J Lamont, Silvia M Uriarte
Filifactor alocis, is a recently recognized periodontal pathogen, however little is known regarding its interactions with the immune system. As the first responder phagocytic cells, neutrophils are recruited in large numbers to the periodontal pocket, where they play a crucial role in the innate defense of the periodontium. Thus, in order to colonize, successful periodontal pathogens must devise means to interfere with neutrophil chemotaxis and activation. In this study, we assessed major neutrophil functions including degranulation and cell migration associated with the p38 MAPK signaling pathway upon challenge with F...
September 19, 2016: Infection and Immunity
Starlee Lively, Sarah Hutchings, Lyanne C Schlichter
Within hours after stroke, potentially cytotoxic pro-inflammatory mediators are elevated within the brain; thus, one potential therapeutic strategy is to reduce them and skew the brain toward an anti-inflammatory state. Because interleukin-4 (IL-4) treatment induces an anti-inflammatory, "alternative-activation" state in microglia and macrophages in vitro, we tested the hypothesis that early supplementation of the brain with IL-4 can shift it toward an anti-inflammatory state and reduce damage after transient focal ischemia...
September 15, 2016: Journal of Neuropathology and Experimental Neurology
Hiroki Ishikawa, Toshie Fukui, Satoshi Ino, Hiraku Sasaki, Naoki Awano, Chikara Kohda, Kazuo Tanaka
The immunological mechanisms of secondary bacterial infection followed by influenza virus infection were examined. When mice were intranasally infected with influenza virus A and then infected with P. aeruginosa at 4 days after viral infection, bacterial clearance in the lung significantly decreased compared to that of non-viral infected mice. Neutrophils from viral infected mice showed impaired digestion and/or killing of phagocytized bacteria due to reduced myeloperoxidase (MPO) activity. G-CSF production in the lungs of viral infected mice was lower than that of non-viral infected mice after secondary bacterial infection...
September 12, 2016: Virology
Yermis Carolina Rocha, Juan Álvaro López, Julio Cesar Orrego, Yadira Coll, Amado Karduss, Sergio Rosenzweig, José Luis Franco
INTRODUCTION: Chronic granulomatous disease is a primary immunodeficiency that results from mutations in proteins of the NADPH oxidase system that affect the microbicidal activity of phagocytes. Immune reconstitution by hematopoietic stem cell transplantation is currently the only curative therapy for this disease.  OBJECTIVE: To describe the clinical and molecular characterization of a patient with X-linked chronic granulomatous disease and the successful immune reconstitution by means of a hematopoietic stem cell transplantation...
2016: Biomédica: Revista del Instituto Nacional de Salud
Nayyer Taheri, Anna Fahlgren, Maria Fällman
Neutrophils are essential components of immunity and are rapidly recruited to infected or injured tissue. Upon their activation, neutrophils release granules to the cell's exterior, through a process called degranulation. These granules contain proteins with antimicrobial properties that help combat infection. The enteropathogenic bacterium, Yersinia pseudotuberculosis, successfully persists as an extracellular bacterium during infection by virtue of its translocation of virulence effectors [Yersinia outer proteins (Yops)] that act in the cytosol of host immune cells to subvert phagocytosis and pro-inflammatory responses...
September 12, 2016: Infection and Immunity
Lorenza Lisa Serena Lanini, Seraina Prader, Ulrich Siler, Janine Reichenbach
Phagocytic neutrophil granulocytes are among the first immune cells active at sites of infection, forming an important first-line defense against invading microorganisms. Congenital immune defects concerning these phagocytes may be due to reduced neutrophil numbers or function. Management of affected patients depends on the type and severity of disease. Here, we provide an overview of causes and treatment of diseases associated with congenital neutropenia, as well as defects of the phagocytic respiratory burst...
September 9, 2016: Pediatric Allergy and Immunology
Bernd Uhl, Yannick Vadlau, Gabriele Zuchtriegel, Katharina Nekolla, Kariem Sharaf, Florian Gaertner, Steffen Massberg, Fritz Krombach, Christoph A Reichel
Under steady-state conditions, aged neutrophils are removed from the circulation in bone marrow, liver, and spleen thereby maintaining myeloid cell homeostasis. The fate of these aged immune cells under inflammatory conditions, however, remains largely obscure. Here, we demonstrate that in the acute inflammatory response during endotoxemia aged neutrophils cease returning to the bone marrow and instead rapidly migrate to the site of inflammation. Having arrived in inflamed tissue, aged neutrophils were found to exhibit a higher phagocytic activity as compared to the subsequently recruited non-aged neutrophils...
September 8, 2016: Blood
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