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neutrophils starvation

Mirjana Jerkic, Michelle Letarte
Endoglin (ENG) is a TGF-β superfamily coreceptor essential for vascular endothelium integrity. ENG mutations lead to a vascular dysplasia associated with frequent hemorrhages in multiple organs, whereas ENG null mouse embryos die at midgestation with impaired heart development and leaky vasculature. ENG interacts with several proteins involved in cell adhesion, and we postulated that it regulates vascular permeability. The current study assessed the permeability of ENG homozygous null (Eng(-/-)), heterozygous (Eng(+/-)), and normal (Eng(+/+)) mouse embryonic endothelial cell (EC) lines...
September 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Andrew G Turner, Cheryl-Lynn Y Ong, Christine M Gillen, Mark R Davies, Nicholas P West, Alastair G McEwan, Mark J Walker
UNLABELLED: Streptococcus pyogenes (group A Streptococcus [GAS]) is an obligate human pathogen responsible for a spectrum of human disease states. Metallobiology of human pathogens is revealing the fundamental role of metals in both nutritional immunity leading to pathogen starvation and metal poisoning of pathogens by innate immune cells. Spy0980 (MntE) is a paralog of the GAS zinc efflux pump CzcD. Through use of an isogenic mntE deletion mutant in the GAS serotype M1T1 strain 5448, we have elucidated that MntE is a manganese-specific efflux pump required for GAS virulence...
2015: MBio
Alina Aguirre, Inés López-Alonso, Adrián González-López, Laura Amado-Rodríguez, Estefanía Batalla-Solís, Aurora Astudillo, Jorge Blázquez-Prieto, Alvaro F Fernández, José A Galván, Claudia C dos Santos, Guillermo M Albaiceta
UNLABELLED: Autophagy has emerged as a key regulator of the inflammatory response. To examine the role of autophagy in the development of organ dysfunction during endotoxemia, wild-type and autophagy-deficient (Atg4b-null) mice were challenged with lipopolysaccharide. Animals lacking Atg4b showed increased mortality after endotoxemia. Among the different organs studied, only the lungs showed significant differences between genotypes, with increased damage in mutant animals. Autophagy was activated in lungs from wild-type, LPS-treated mice...
June 2014: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Sylvia Simon, Maria A Wagner, Eva Rothmeier, Annette Müller-Taubenberger, Hubert Hilbi
The environmental bacterium Legionella pneumophila causes a severe pneumonia termed Legionnaires' disease. L. pneumophila employs a conserved mechanism to replicate within a specific vacuole in macrophages or protozoa such as the social soil amoeba Dictyostelium discoideum. Pathogen-host interactions depend on the Icm/Dot type IV secretion system (T4SS), which translocates approximately 300 different effector proteins into host cells. Here we analyse the effects of L. pneumophila on migration and chemotaxis of amoebae, macrophages or polymorphonuclear neutrophils (PMN)...
July 2014: Cellular Microbiology
Fraser D Russell, Karina D Hamilton
Nutrient deprivation is a stimulus for oxidative stress and is an established method for induction of cell autophagy and apoptosis. The aims of this study were to identify conditions that evoke superoxide production in cultured human umbilical vein endothelial cells (HUVECs), determine the mechanism of action for this response, and examine whether the stimulus might facilitate the adhesion of human isolated neutrophils to the HUVECs. HUVECs were incubated in M199 medium under conditions of serum starvation (serum-free M199 medium), low serum (medium containing 2% fetal calf serum), and high serum (medium containing 20% fetal calf serum)...
February 2014: Free Radical Biology & Medicine
Jin Wang, Xiangmei Zhou, Bo Pan, Lifeng Yang, Xiaomin Yin, Binrui Xu, Deming Zhao
Bovine tuberculosis is a disease in cattle caused by infection with Mycobacterium bovis. The disease has posed significant economic losses and remains a public health hazard worldwide. Interactions between M. bovis and bovine macrophages have been extensively characterized in various studies, while similar analyses in neutrophils, which are one of the other types of white blood cells in mammals, were often overlooked. Neutrophils provide defense against all microbes and can present a diverse collection of antimicrobial molecules, which play an important role in the control of tuberculosis progression...
November 2013: Tuberculosis
Pedro Miramón, Christine Dunker, Hanna Windecker, Iryna M Bohovych, Alistair J P Brown, Oliver Kurzai, Bernhard Hube
Neutrophils are key players during Candida albicans infection. However, the relative contributions of neutrophil activities to fungal clearance and the relative importance of the fungal responses that counteract these activities remain unclear. We studied the contributions of the intra- and extracellular antifungal activities of human neutrophils using diagnostic Green Fluorescent Protein (GFP)-marked C. albicans strains. We found that a carbohydrate starvation response, as indicated by up-regulation of glyoxylate cycle genes, was only induced upon phagocytosis of the fungus...
2012: PloS One
Abderrahman Chargui, Annabelle Cesaro, Sanda Mimouna, Mohamed Fareh, Patrick Brest, Philippe Naquet, Arlette Darfeuille-Michaud, Xavier Hébuterne, Baharia Mograbi, Valérie Vouret-Craviari, Paul Hofman
Invading bacteria are recognized, captured and killed by a specialized form of autophagy, called xenophagy. Recently, defects in xenophagy in Crohn's disease (CD) have been implicated in the pathogenesis of human chronic inflammatory diseases of uncertain etiology of the gastrointestinal tract. We show here that pathogenic adherent-invasive Escherichia coli (AIEC) isolated from CD patients are able to adhere and invade neutrophils, which represent the first line of defense against bacteria. Of particular interest, AIEC infection of neutrophil-like PLB-985 cells blocked autophagy at the autolysosomal step, which allowed intracellular survival of bacteria and exacerbated interleukin-8 (IL-8) production...
2012: PloS One
Yoon Shin Park, Goh-Woon Lim, Kyung-Ah Cho, So-Youn Woo, Meeyoung Shin, Eun-Sun Yoo, Jeong Chan Ra, Kyung-Ha Ryu
Neutropenia is a principal complication of cancer treatment. We investigated the supportive effect of adipose tissue-derived mesenchymal stem cells (AD-MSCs) on the viability and function of neutrophils. Neutrophils were derived from HL-60 cells by dimethylformamide stimulation and cultured with or without AD-MSCs under serum-starved conditions to evaluate neutrophil survival, proliferation, and function. Serum starvation resulted in the apoptosis of neutrophils and decreased cell survival. The co-culture of neutrophils and AD-MSCs resulted in cell survival and inhibited neutrophil apoptosis under serum-starved conditions...
June 22, 2012: Biochemical and Biophysical Research Communications
Gayathri Subramanian, Pulkit Chaudhury, Krishnakumar Malu, Samantha Fowler, Rahul Manmode, Deepali Gotur, Monika Zwerger, David Ryan, Rita Roberti, Peter Gaines
Lamin B receptor (LBR) is a bifunctional nuclear membrane protein with N-terminal lamin B and chromatin-binding domains plus a C-terminal sterol Δ(14) reductase domain. LBR expression increases during neutrophil differentiation, and deficient expression disrupts neutrophil nuclear lobulation characteristic of Pelger-Huët anomaly. Thus, LBR plays a critical role in regulating myeloid differentiation, but how the two functional domains of LBR support this role is currently unclear. We previously identified abnormal proliferation and deficient functional maturation of promyelocytes (erythroid, myeloid, and lymphoid [EML]-derived promyelocytes) derived from EML-ic/ic cells, a myeloid model of ichthyosis (ic) bone marrow that lacks Lbr expression...
January 1, 2012: Journal of Immunology: Official Journal of the American Association of Immunologists
Christopher A McDevitt, Abiodun D Ogunniyi, Eugene Valkov, Michael C Lawrence, Bostjan Kobe, Alastair G McEwan, James C Paton
Transition row metal ions are both essential and toxic to microorganisms. Zinc in excess has significant toxicity to bacteria, and host release of Zn(II) at mucosal surfaces is an important innate defence mechanism. However, the molecular mechanisms by which Zn(II) affords protection have not been defined. We show that in Streptococcus pneumoniae extracellular Zn(II) inhibits the acquisition of the essential metal Mn(II) by competing for binding to the solute binding protein PsaA. We show that, although Mn(II) is the high-affinity substrate for PsaA, Zn(II) can still bind, albeit with a difference in affinity of nearly two orders of magnitude...
November 2011: PLoS Pathogens
Xuehua Xu, Tian Jin
Many eukaryotic cells can detect gradients of chemical signals in their environments and migrate accordingly (1). This guided cell migration is referred as chemotaxis, which is essential for various cells to carry out their functions such as trafficking of immune cells and patterning of neuronal cells (2, 3). A large family of G-protein coupled receptors (GPCRs) detects variable small peptides, known as chemokines, to direct cell migration in vivo (4). The final goal of chemotaxis research is to understand how a GPCR machinery senses chemokine gradients and controls signaling events leading to chemotaxis...
2011: Journal of Visualized Experiments: JoVE
Jimena Alvarez Hayes, Esteban Erben, Yanina Lamberti, Miguel Ayala, Fabricio Maschi, Cecilia Carbone, Blanca Gatti, Gustavo Parisi, Maria Eugenia Rodriguez
Antigenic proteins whose expression is induced under iron starvation, an environmental condition that bacterial pathogens have to face during colonization, might be potential candidates for improved vaccine. By mean of immune proteomics we identified novel antigens of Bordetella pertussis maximally expressed under iron limitation. Among them, Bp1152 (named as IRP1-3) showed a particularly strong reaction with human IgG purified from pooled sera of pertussis-infected individuals. Computer analysis showed IRP1-3 as a dimeric membrane protein potentially involved in iron uptake...
November 3, 2011: Vaccine
Matteo Bianchi, Maria J Niemiec, Ulrich Siler, Constantin F Urban, Janine Reichenbach
BACKGROUND: Aspergillus spp infection is a potentially lethal disease in patients with neutropenia or impaired neutrophil function. We showed previously that Aspergillus hyphae, too large for neutrophil phagocytosis, are inhibited by reactive oxygen species-dependent neutrophil extracellular trap (NET) formation. This process is defective in chronic granulomatous disease (CGD) because of impaired phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase function. OBJECTIVE: To determine the antifungal agent and mechanism responsible for reconstitution of Aspergillus growth inhibition within NETs after complementation of NADPH oxidase function by gene therapy (GT) for CGD...
May 2011: Journal of Allergy and Clinical Immunology
Sanjeev Kumar, David A Allen, Julius E Kieswich, Nimesh S A Patel, Steven Harwood, Emanuela Mazzon, Salvatore Cuzzocrea, Martin J Raftery, Christoph Thiemermann, Muhammad M Yaqoob
In the setting of renal ischemia-reperfusion injury (IRI), the effect and mechanism of action of glucocorticoids are not well understood. In rat renal IRI, a single dose of dexamethasone administered before ischemia, or at the onset of reperfusion, ameliorated biochemical and histologic acute kidney injury after 24 h. Dexamethasone upregulated Bcl-xL, downregulated ischemia-induced Bax, inhibited caspase-9 and caspase-3 activation, and reduced apoptosis and necrosis of proximal tubular cells. In addition, dexamethasone decreased the number of infiltrating neutrophils and ICAM-1...
November 2009: Journal of the American Society of Nephrology: JASN
C Rummel, W Inoue, S Poole, G N Luheshi
The appetite suppressing hormone leptin has emerged as an important modulator of immune function and is now considered to be a critical link between energy balance and host defense responses to pathogens. These 'adaptive' responses can, in situations of severe and sustained systemic inflammation, lead to adverse effects including brain damage that is partly mediated by neutrophil recruitment into the brain. We examined the contribution of leptin to this process in leptin-deficient (ob/ob), -resistant (db/db) and wild-type (WT) mice injected intraperitoneally with a septic dose of lipopolysaccharide (LPS)...
May 2010: Molecular Psychiatry
John A Hanover, Michael W Krause, Dona C Love
The enzymes of O-GlcNAc cycling couple the nutrient-dependent synthesis of UDP-GlcNAc to O-GlcNAc modification of Ser/Thr residues of key nuclear and cytoplasmic targets. This series of reactions culminating in O-GlcNAcylation of targets has been termed the hexosamine signaling pathway (HSP). The evolutionarily ancient enzymes of O-GlcNAc cycling have co-evolved with other signaling effecter molecules; they are recruited to their targets by many of the same mechanisms used to organize canonic kinase-dependent signaling pathways...
February 2010: Biochimica et Biophysica Acta
Andrew McDonagh, Natalie D Fedorova, Jonathan Crabtree, Yan Yu, Stanley Kim, Dan Chen, Omar Loss, Timothy Cairns, Gustavo Goldman, Darius Armstrong-James, Ken Haynes, Hubertus Haas, Markus Schrettl, Gregory May, William C Nierman, Elaine Bignell
Aspergillus fumigatus is a common mould whose spores are a component of the normal airborne flora. Immune dysfunction permits developmental growth of inhaled spores in the human lung causing aspergillosis, a significant threat to human health in the form of allergic, and life-threatening invasive infections. The success of A. fumigatus as a pathogen is unique among close phylogenetic relatives and is poorly characterised at the molecular level. Recent genome sequencing of several Aspergillus species provides an exceptional opportunity to analyse fungal virulence attributes within a genomic and evolutionary context...
2008: PLoS Pathogens
C Haanen, I Vermes
During the last few decades it has been recognized that cell death is not the consequence of accidental injury, but is the expression of a cell suicide programme. Kerr et al. (1972) introduced the term apoptosis. This form of cell death is under the influence of hormones, growth factors and cytokines, which depending upon the receptors present on the target cells, may activate a genetically controlled cell elimination process. During apoptosis the cell membrane remains intact and the cell breaks into apoptotic bodies, which are phagocytosed...
1995: Mediators of Inflammation
Shi Shu, Dana C Mahadeo, Xiong Liu, Wenli Liu, Carole A Parent, Edward D Korn
Chemotaxis of bacteria requires regulated methylation of chemoreceptors. However, despite considerable effort in the 1980s, transmethylation has never been established as a component of eukaryotic cell chemotaxis. S-adenosylhomocysteine (SAH), the product formed when the methyl group of the universal donor S-adenosylmethionine (SAM) is transferred to an acceptor molecule, is a potent inhibitor of all transmethylation reactions. In eukaryotic cells, this inhibition is relieved by hydrolysis of SAH to adenosine and homocysteine catalyzed by SAH hydrolase (SAHH)...
December 26, 2006: Proceedings of the National Academy of Sciences of the United States of America
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