Genomes and Genes
Summary: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
Publications267 found, 100 shown here
- Neutrophil extracellular traps kill bacteriaVolker Brinkmann
Microscopy Core Facility, Max Planck Institute for Infection Biology, Schumannstrasse 21/22, 10117 Berlin, Germany
Science 303:1532-5. 2004b>Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome...
- Neutrophils, from marrow to microbesNiels Borregaard
The Granulocyte Research Laboratory, Department of Hematology, National University Hospital Rigshospitalet, University of Copenhagen, DK 2100 Copenhagen, Denmark
Immunity 33:657-70. 2010b>Neutrophils are produced in the bone marrow from stem cells that proliferate and differentiate to mature neutrophils fully equipped with an armory of granules...
- Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide productionJ D Pollock
Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indianapolis, Indiana, USA
Nat Genet 9:202-9. 1995..This animal model should aid in developing new treatments for CGD and in evaluating the role of phagocyte-derived oxidants in inflammation...
- Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in miceTerrence M Tumpey
Influenza Branch, Mail Stop G 16, DVRD, NCID, Centers for Disease Control and Prevention, 1600 Clifton Road, N E, Atlanta, GA 30333, USA
J Virol 79:14933-44. 2005..mice was accompanied by (i) increased (>200-fold) viral replication, (ii) greater influx of neutrophils into the lung, (iii) increased numbers of alveolar macrophages (AMs), and (iv) increased protein expression of ..
- Glucocorticoids induce protein S-dependent phagocytosis of apoptotic neutrophils by human macrophagesAisleen McColl
Medical Research Council Centre for Inflammation Research, Queen s Medical Research Institute, Edinburgh, United Kingdom
J Immunol 183:2167-75. 2009..containing C4-binding protein and protein S responsible for the augmentation of phagocytosis of apoptotic neutrophils. Because the apoptotic neutrophils used in this study specifically bind protein S, we suggest that ..
- Intravascular danger signals guide neutrophils to sites of sterile inflammationBraedon McDonald
Immunology Research Group, University of Calgary, Alberta T2N 4N1, Canada
Science 330:362-6. 2010b>Neutrophils are recruited from the blood to sites of sterile inflammation, where they contribute to wound healing but may also cause tissue damage...
- Production of extracellular traps against Aspergillus fumigatus in vitro and in infected lung tissue is dependent on invading neutrophils and influenced by hydrophobin RodASandra Bruns
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology Hans Knoell Institute HKI, Jena, Germany
PLoS Pathog 6:e1000873. 2010..Macrophages and neutrophils are known to kill conidia, whereas hyphae are killed mainly by neutrophils...
- NETs: a new strategy for using old weaponsVenizelos Papayannopoulos
Department for Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
Trends Immunol 30:513-21. 2009As key players in the host innate immune response, neutrophils are recruited to sites of infection and constitute the first line of defense...
- Severity of E. coli mastitis is mainly determined by cow factorsChristian Burvenich
Mammary gland and Mastitis Research Centre, Department of Physiology, Biochemistry and Biometrics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
Vet Res 34:521-64. 2003..coli. Effective elimination of the pathogen by neutrophils is important for the resolution of infection and the outcome of E. coli mastitis...
- Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signalsFlavia Bazzoni
Department of Pathology, Division of General Pathology, University of Verona, Strada Le Grazie 8, I 37134 Verona, Italy
Proc Natl Acad Sci U S A 106:5282-7. 2009..In this study, we characterize the profile of miRNAs induced by LPS in human polymorphonuclear neutrophils (PMN) and monocytes...
- Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicansConstantin F Urban
Department for Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
PLoS Pathog 5:e1000639. 2009b>Neutrophils are the first line of defense at the site of an infection...
- Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitisJiyun V Kim
Program in Molecular Pathogenesis, Helen L and Martin S Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
Nature 457:191-5. 2009..Here we report visualization of motile CTLs and massive secondary recruitment of pathogenic monocytes and neutrophils that were required for vascular leakage and acute lethality...
- Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathologyDe Broski R Herbert
University of Cape Town, Health Sciences Faculty, 7925 Cape Town, South Africa
Immunity 20:623-35. 2004..Mortality was not dependent on neutrophils and occurred in the presence of T(H)2/Type 2 responses, granuloma formation, and egg-induced fibrosis...
- Neutrophils ameliorate lung injury and the development of severe disease during influenza infectionMichelle D Tate
Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia
J Immunol 183:7441-50. 2009..We have defined a novel role for neutrophils in ameliorating lung injury during influenza infection, thereby limiting development of severe disease...
- CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrowKyle J Eash
Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110, USA
J Clin Invest 120:2423-31. 2010b>Neutrophils are a major component of the innate immune response. Their homeostasis is maintained, in part, by the regulated release of neutrophils from the bone marrow...
- The cyclin-dependent kinase inhibitor R-roscovitine down-regulates Mcl-1 to override pro-inflammatory signalling and drive neutrophil apoptosisAndrew E Leitch
MRC Centre for Inflammation Research, The Queen s Medical Research Institute, University of Edinburgh Medical School, Edinburgh, Scotland, UK
Eur J Immunol 40:1127-38. 2010Successful resolution of inflammation requires inflammatory cells such as neutrophils to undergo apoptosis prior to non-inflammatory phagocytosis by professional phagocytes. Recently, cyclin-dependent kinase (CDK) inhibitors (e.g...
- Yersinia pestis two-component gene regulatory systems promote survival in human neutrophilsJason L O'Loughlin
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA
Infect Immun 78:773-82. 2010Human polymorphonuclear leukocytes (PMNs, or neutrophils) are the most abundant innate immune cell and kill most invading bacteria through combined activities of reactive oxygen species (ROS) and antimicrobial granule constituents...
- A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureusFlorian H Pilsczek
Snyder Institute of Infection, Immunity and Inflammation, Hiroshima University, Hiroshima, Japan
J Immunol 185:7413-25. 2010..reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET ..
- Differential inflammatory activity across human abdominal aortic aneurysms reveals neutrophil-derived leukotriene B4 as a major chemotactic factor released from the intraluminal thrombusXavier Houard
INSERM U698, Paris 7 Denis Diderot University, Cardiovascular Hematology, Bio Engineering and Remodeling, Bichat Claude Bernard Hospital, 75877 Paris Cedex 18, France
FASEB J 23:1376-83. 2009..and LTA(4) hydrolase, as well as the two receptors for leukotriene B(4) (BLT1R and BLT2R), corresponding to neutrophils in the luminal part of the thrombus...
- Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic bloodStephen R Clark
Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada
Nat Med 13:463-9. 2007It has been known for many years that neutrophils and platelets participate in the pathogenesis of severe sepsis, but the inter-relationship between these players is completely unknown...
- Neutrophils and immunity: challenges and opportunitiesCarl Nathan
Department of Microbiology and Immunology, Weill Cornell Medical College, Weill Graduate School of Medical Sciences of Cornell University, Box 57, 1300 York Avenue, New York 10021, USA
Nat Rev Immunol 6:173-82. 2006Scientists who study neutrophils often have backgrounds in cell biology, biochemistry, haematology, rheumatology or infectious disease...
- The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infectionMilan Chromek
Department of Clinical Microbiology, Microbiology and Tumorbiology Center, Karolinska University Hospital and Karolinska Institutet, SE 171 76 Stockholm, Sweden
Nat Med 12:636-41. 2006..In addition, clinical E. coli strains that were more resistant to LL-37 caused more severe urinary tract infections than did susceptible strains. Thus, cathelicidin seems to be a key factor in mucosal immunity of the urinary tract...
- Neutrophils play an important role in host resistance to respiratory infection with Acinetobacter baumannii in miceHenk van Faassen
Institute for Biological Sciences, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada
Infect Immun 75:5597-608. 2007..In this study, we examined the role of neutrophils in host resistance to pulmonary A. baumannii infection in a mouse model of intranasal (i.n.) infection...
- A paradoxical role for neutrophils in the pathogenesis of West Nile virusFengwei Bai
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8031, USA
J Infect Dis 202:1804-12. 2010..Collectively, these data suggest that PMNs have a biphasic response to WNV infection, serving as a reservoir for replication and dissemination in early infection and later contributing to viral clearance...
- Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular trapsVenizelos Papayannopoulos
Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
J Cell Biol 191:677-91. 2010b>Neutrophils release decondensed chromatin termed neutrophil extracellular traps (NETs) to trap and kill pathogens extracellularly...
- Neutrophil apoptosis: a target for enhancing the resolution of inflammationJanos G Filep
Research Center, Maisonneuve Rosemont Hospital, Department of Pathology and Cell Biology, University of Montreal, Montreal, Quebec, Canada
J Cell Biochem 108:1039-46. 2009b>Neutrophils are essential for host defense and their programmed cell death and removal are critical for the optimal expression as well as for efficient resolution of inflammation...
- A new pathway of staphylococcal pathogenesis: apoptosis-like death induced by Staphopain B in human neutrophils and monocytesJan Smagur
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
J Innate Immun 1:98-108. 2009Circulating neutrophils and monocytes form the first line of cellular defense against invading bacteria. Here, we describe a novel and specific mechanism of disabling and eliminating phagocytes by Staphylococcus aureus...
- Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor modelJadwiga Jablonska
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
J Clin Invest 120:1151-64. 2010..tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-beta-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells ..
- CFTR-mediated halide transport in phagosomes of human neutrophilsRichard G Painter
Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
J Leukoc Biol 87:933-42. 2010..against infection, providing the substrate for MPO-catalyzed production of HOCl in the phagosome of human neutrophils. Here, we used halide-specific fluorescent sensors covalently coupled to zymosan particles to investigate the ..
- Rapid neutrophil destruction following phagocytosis of Staphylococcus aureusScott D Kobayashi
Laboratory of Human Bacterial Pathogenesis, Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
J Innate Immun 2:560-75. 2010..incompletely defined, but presumably include evasion of killing by human polymorphonuclear leukocytes (PMNs or neutrophils)...
- Lipid-cytokine-chemokine cascade drives neutrophil recruitment in a murine model of inflammatory arthritisRichard C Chou
Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Immunity 33:266-78. 2010..We now demonstrate that BLT1 is required for neutrophils to deliver IL-1 into the joint to initiate arthritis...
- Recent developments and complexities in neutrophil transmigrationAbigail Woodfin
Queen Mary University of London, William Harvey Research Institute, UK
Curr Opin Hematol 17:9-17. 2010As the migration of neutrophils from blood to inflamed tissues is an essential component of innate immunity and a key contributing factor to the pathogenesis of inflammatory disorders, this aspect of leukocyte biology continues to be a ..
- Regulation of neutrophil apoptosis by Mcl-1S W Edwards
School of Biological Sciences, University of Liverpool, Liverpool L60 7ZB, UK
Biochem Soc Trans 32:489-92. 2004b>Neutrophils rapidly undergo spontaneous apoptosis, but this process can be considerably delayed by exposure to a variety of agents such as pro-inflammatory cytokines...
- Neutrophils and the pathogenesis of COPDRobert A Stockley
Lung Resource Center, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK
Chest 121:151S-155S. 2002
- Use of Ly6G-specific monoclonal antibody to deplete neutrophils in miceJean M Daley
Department of Surgery, Division of Surgical Research, Rhode Island Hospital, NAB 214, 593 Eddy Street, Providence, RI 02903, USA
J Leukoc Biol 83:64-70. 2008The anti-granulocyte receptor-1 (Gr-1) mAb, RB6-8C5, has been used extensively to deplete neutrophils in mice and to investigate the role of these cells in host defense...
- Suppression of Fas-FasL-induced endothelial cell apoptosis prevents diabetic blood-retinal barrier breakdown in a model of streptozotocin-induced diabetesAntonia M Joussen
Retina Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA
FASEB J 17:76-8. 2003..Following the onset of streptozotocin-induced diabetes, FasL expression was increased in rat neutrophils (P<0.005) and was accompanied by a simultaneous increase in Fas expression in the retinal vasculature...
- Role of neutrophils in a mouse model of halothane-induced liver injuryQiang You
Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO 80262, USA
Hepatology 44:1421-31. 2006..Moreover, a higher number of neutrophils were recruited into the liver of Balb/c mice upon halothane treatment compared with DBA/1, with no obvious ..
- Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repairJing Zhu
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA
Cell 111:867-78. 2002..Supplying PEPI corrects the wound-healing defect in SLPI null mice. Thus, SLPI/elastase act via PEPI/EPIs to operate a switch at the interface between innate immunity and wound healing...
- CFTR Expression in human neutrophils and the phagolysosomal chlorination defect in cystic fibrosisRichard G Painter
Gene Therapy Program, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
Biochemistry 45:10260-9. 2006Production of hypochlorous acid (HOCl) in neutrophils, a critical oxidant involved in bacterial killing, requires chloride anions...
- Compromised host defense on Pseudomonas aeruginosa biofilms: characterization of neutrophil and biofilm interactionsAlgirdas J Jesaitis
Department of Microbiology, Montana State University, Bozeman, MT 59717 3520, USA
J Immunol 171:4329-39. 2003..We characterized the interaction of purified human neutrophils with P...
- Neutrophils are associated with capillary closure in spontaneously diabetic monkey retinasSahng Y Kim
Wilmer Ophthalmological Institute, Johns Hopkins Hospital, 170 Woods Research Bldg, 600 North Wolfe St, Baltimore, MD 21287-9115, USA
Diabetes 54:1534-42. 2005..Retinas were incubated for ADPase (labels viable retinal blood vessels) and nonspecific esterase (labels neutrophils) activities. Polymorphonuclear leukocytes were counted per millimeter squared of retina...
- Characterization of the tuberculous granuloma in murine and human lungs: cellular composition and relative tissue oxygen tensionMing C Tsai
Department of Medicinem Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
Cell Microbiol 8:218-32. 2006..The kinetics of recruitment of neutrophils, macrophages, dendritic cells, and T and B lymphocytes into the lungs of mice infected aerogenically with the ..
- Interplay between IFN-gamma and IL-6 signaling governs neutrophil trafficking and apoptosis during acute inflammationRachel M McLoughlin
Institute of Nephrology, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, United Kingdom
J Clin Invest 112:598-607. 2003Regulated recruitment and clearance of neutrophils (PMN) is the hallmark of competent host defense and resolution of inflammation...
- Hematologic profile of sepsis in neonates: neutrophil CD64 as a diagnostic markerVineet Bhandari
Department of Pediatrics, Division of Perinatal Medicine, Yale University School of Medicine, LCI 401B, PO Box 208064, New Haven, CT 06520 8064, USA
Pediatrics 121:129-34. 2008..The goal was to determine the utility of neutrophil CD64 as a diagnostic marker for sepsis in neonates...
- Humoral and cell-mediated immunity to the intracellular pathogen Francisella tularensisGirish S Kirimanjeswara
Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA
Immunol Rev 225:244-55. 2008..tularensis. Thus, novel vaccine approaches should be designed to induce robust antibody and cell-mediated immune responses to this pathogen...
- Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytesPaulo C Rodriguez
Department of Microbiology, Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
Cancer Res 69:1553-60. 2009..These results may provide new insights on the mechanisms of tumor-induced anergy/tolerance and may help explain why some immunotherapies fail to induce an antitumor response...
- Circulating mitochondrial DAMPs cause inflammatory responses to injuryQin Zhang
Department of Surgery, Division of Trauma, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Nature 464:104-7. 2010..MTDs include formyl peptides and mitochondrial DNA. These activate human polymorphonuclear neutrophils (PMNs) through formyl peptide receptor-1 and Toll-like receptor (TLR) 9, respectively...
- Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophilsO Chertov
Laboratory of Molecular Immunoregulation, Biological Response Modifiers Program, Division of Cancer Treatment, NCI, National Institutes of Health, Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA
J Biol Chem 271:2935-40. 1996Reports that interleukin-8 (IL-8) induces the infiltration of neutrophils followed by T-cells into injection sites led us to postulate that by stimulation of neutrophil degranulation IL-8 may cause the release of factors with ..
- The phagocytes: neutrophils and monocytesDavid C Dale
Department of Medicine, University of Washington School of Medicine, Seattle A98195, USA
Blood 112:935-45. 2008..In the 1950s, radioisotopic studies demonstrated the high production rate and short lifespan of neutrophils and allowed researchers to follow the monocytes as they moved from the marrow through the blood to become ..
- Evidence for a cross-talk between human neutrophils and Th17 cellsMartin Pelletier
Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy
Blood 115:335-43. 2010..several cytokines produced by T helper 17 cells (Th17), which are able to indirectly induce the recruitment of neutrophils. Recently, human Th17 cells have been phenotypically characterized and shown to express discrete chemokine ..
- Clinical trial of doxycycline for matrix metalloproteinase-9 inhibition in patients with an abdominal aneurysm: doxycycline selectively depletes aortic wall neutrophils and cytotoxic T cellsJan H N Lindeman
Department of Vascular Surgery, K6R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
Circulation 119:2209-16. 2009..We thus hypothesized that doxycycline acts through an effect on vascular inflammation...
- IL-17 produced by neutrophils regulates IFN-gamma-mediated neutrophil migration in mouse kidney ischemia-reperfusion injuryLi Li
Department of Medicine, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia 22908, USA
J Clin Invest 120:331-42. 2010..We further demonstrate that IL-17A produced by GR-1+ neutrophils was critical for kidney IRI in mice...
- Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2Richard E Person
Department of Pathology, University of Washington School of Medicine, Box 357720, Seattle, Washington 98195, USA
Nat Genet 34:308-12. 2003....
- Transepithelial migration of neutrophils: mechanisms and implications for acute lung injuryRachel L Zemans
Division of Pulmonary and Critical Care Medicine, Department of Medicine, National Jewish Health, Denver, CO 80206, USA
Am J Respir Cell Mol Biol 40:519-35. 2009The primary function of neutrophils in host defense is to contain and eradicate invading microbial pathogens...
- The role of chloride anion and CFTR in killing of Pseudomonas aeruginosa by normal and CF neutrophilsRichard G Painter
Gene Therapy Program, Department of Medicine and Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
J Leukoc Biol 83:1345-53. 2008Chloride anion is essential for myeloperoxidase (MPO) to produce hypochlorous acid (HOCl) in polymorphonuclear neutrophils (PMNs)...
- The role of Toll-like receptors in the regulation of neutrophil migration, activation, and apoptosisIan Sabroe
Division of Genomic Medicine, School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, UK
Clin Infect Dis 41:S421-6. 2005..this signal is greatly amplified by the presence of monocytes, suggesting that regulation of the life span of neutrophils by TLR agonists may be principally mediated by responses of other endotoxin-responsive cells...
- LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells- De Yang
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, Frederick, MD, USA
J Exp Med 192:1069-74. 2000..LL-37/hCAP18 is produced by neutrophils and various epithelial cells...
- Anthrax toxins inhibit neutrophil signaling pathways in brain endothelium and contribute to the pathogenesis of meningitisNina M van Sorge
Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America
PLoS ONE 3:e2964. 2008..barrier but has been shown to play an active role in initiating a specific innate immune response that recruits neutrophils to the site of infection. Currently, the basic pathogenic mechanisms by which B...
- The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of miceMichelle D Tate
Department of Microbiology and Immunology, The University of Melbourne, Parkville, 3010, Victoria, Australia
Respir Res 9:57. 2008b>Neutrophils have been shown to play a role in host defence against highly virulent and mouse-adapted strains of influenza virus, however it is not clear if an effective neutrophil response is an important factor moderating disease ..
- Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: a critical role for monocytes in leukocyte lipopolysaccharide responsesIan Sabroe
Section of Functional Genomics, Division of Genomic Medicine, University of Sheffield, Sheffield, United Kingdom
J Immunol 168:4701-10. 2002Leukocyte responsiveness to LPS is dependent upon CD14 and receptors of the Toll-like receptor (TLR) family. Neutrophils respond to LPS, but conflicting data exist regarding LPS responses of eosinophils and basophils, and expression of ..
- Neutrophil-mediated innate immune resistance to mycobacteriaAdrian R Martineau
Wellcome Trust Center for Research in Clinical Tropical Medicine, Division of Medicine, Wright Fleming Institute, Imperial College, London, UK
J Clin Invest 117:1988-94. 2007b>Neutrophils contain antimicrobial peptides with antituberculous activity, but their contribution to immune resistance to tuberculosis (TB) infection has not been previously investigated to our knowledge...
- Heterogeneity of airway inflammation in persistent asthma : evidence of neutrophilic inflammation and increased sputum interleukin-8P G Gibson
Airways Research Centre, Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia
Chest 119:1329-36. 2001..To identify the characteristics of airway inflammation in persistent asthma and to examine the role of neutrophilic inflammation in noneosinophilic persistent asthma...
- Epidermal growth factor enhances TNF-alpha-induced priming of human neutrophilsPrzemysław Lewkowicz
Department of Clinical Immunology, Institute of Polish Mother s Memorial Hospital, ul Rzgowska 281 289, 93 338 Lodz, Poland
Immunol Lett 96:203-10. 2005..We proposed that epidermal growth factor (EGF) increases TNF-alpha-induced priming of human neutrophils. This study showed that EGF enhanced TNF-alpha-induced activation of neutrophils functions...
- Heterogeneity of functional responses in differentiated myeloid cell lines reveals EPRO cells as a valid model of murine neutrophil functional activationPeter Gaines
Section of Hematology, WWW 428, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
J Leukoc Biol 77:669-79. 2005Mature neutrophils display multiple functional responses upon activation that include chemotaxis, adhesion to and transmigration across endothelial cells, phagocytosis, and pathogen destruction via potent microbicidal enzymes and ..
- Myeloperoxidase: friend and foeSeymour J Klebanoff
Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195 7185, USA
J Leukoc Biol 77:598-625. 2005Neutrophilic polymorphonuclear leukocytes (neutrophils) are highly specialized for their primary function, the phagocytosis and destruction of microorganisms...
- Neutrophils accelerate macrophage-mediated digestion of apoptotic cells in vivo as well as in vitroTakuya Iyoda
Division of Molecular Medicine, Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Japan
J Immunol 175:3475-83. 2005..into the peritoneal cavity induced the expression of an inflammatory chemokine, MIP-2, and infiltration of neutrophils, and that anti-MIP-2 Abs suppressed the infiltration significantly...
- Migration of polymorphonuclear leucocytes is influenced by dendritic cellsM Lucila Scimone
, , , , Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Immunology 114:375-85. 2005..Furthermore, our results also suggest that CXCL8 production by immature DCs might be regulated by signalling through CD31 during their migration through the vascular endothelium...
- Failure of neutrophil chemotactic function in breast cancer patients treated with chemotherapyMaria Angélica O Mendonça
Department of Biological Sciences, Faculty of Medicine of Triangulo Mineiro, Praça Manoel Terra, 330, CEP, 38015 050, Uberaba MG, Brazil
Cancer Chemother Pharmacol 57:663-70. 2006..Herein, we investigated the effect of chemotherapy on the migration capacity of circulating neutrophils obtained from breast cancer patients and mechanisms involved in this event...
- Neutrophil dysfunction in guanosine 3',5'-cyclic monophosphate-dependent protein kinase I-deficient miceClaudia G Werner
Institut fur Pharmakologie und Toxikologie, Technische Universitat Munchen, Munchen, Germany
J Immunol 175:1919-29. 2005..We demonstrate that murine neutrophils expressed cGKIalpha...
- Innate immune traits differ between Meishan and Large White pigsM Clapperton
Department of Genomics and Bioinformatics, Roslin Institute, Roslin, Midlothian, Edinburgh EH25 9PS, UK
Vet Immunol Immunopathol 104:131-44. 2005..Total white cell counts were similar between the pig breeds. However, the numbers of lymphocytes, neutrophils and monocytes differed significantly, with Meishans having higher neutrophil and monocyte counts and lower ..
- Respiratory syncytial virus and neutrophil activationE L Bataki
Department of Respiratory Medicine, Sheffield Children's Hospital, Sheffield, UK
Clin Exp Immunol 140:470-7. 2005Respiratory syncytial virus infects almost all children by 2 years of age. Neutrophils are the predominant airway leucocytes in RSV bronchiolitis and they are activated in the presence of infection...
- Fish oil before cardiac surgery: neutrophil activation is unaffected but myocardial damage is moderatedA Charman
Centre for Nutrition and Food Research, Queen Margaret University College, Edinburgh EH12 8TS, UK
Prostaglandins Leukot Essent Fatty Acids 72:257-65. 2005..Area-under-the-curve analysis did not conclusively support this (P=0.068). We conclude that fish oil did not significantly decrease post-CPB neutrophil activation (as detected ex vivo) but may moderate post-operative myocardial damage...
- ADAM17 activity during human neutrophil activation and apoptosisBruce Walcheck
Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, MN 55108, USA
Eur J Immunol 36:968-76. 2006..polymorphonuclear leukocytes contribute significantly to inflammation, direct analyses of ADAM17 on human neutrophils are very limited...
- Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndromePatricia Redecha
Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York, USA
J Clin Invest 118:3453-61. 2008..We have previously shown that C5a induction of tissue factor (TF) expression in neutrophils contributes to respiratory burst, trophoblast injury, and pregnancy loss in mice treated with aPL...
- A novel proteolytic cascade generates an extracellular matrix-derived chemoattractant in chronic neutrophilic inflammationAmit Gaggar
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
J Immunol 180:5662-9. 2008..matrix-derived neutrophil chemoattractant, proline-glycine-proline (PGP), acts through CXC receptors 1 and 2 on neutrophils, similar to N-acetylated proline-glycine-proline (N-alpha-PGP)...
- Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulinKai Kessenbrock
Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany
J Clin Invest 118:2438-47. 2008..immune complex-mediated (IC-mediated) neutrophil infiltration in vivo as well as reduced activation of isolated neutrophils by ICs in vitro...
- The intriguing normal acute inflammatory response in mice lacking vimentinE Moisan
INRS Institut Armand Frappier, Universite du Quebec, Pointe Claire, PQ, Canada
Clin Exp Immunol 150:158-68. 2007b>Neutrophils express only two intermediate filament proteins, vimentin and, to a lesser extent, lamin B. Lamin B mutant mice die shortly after birth; however, mice lacking vimentin (vim(-/-)) develop and reproduce normally...
- Sequential chemotactic and phagocytic activation of human polymorphonuclear neutrophilsJens Martin Herrmann
Department of Biochemistry, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118, USA
Infect Immun 75:3989-98. 2007Human polymorphonuclear neutrophils (PMN) chemotax to a foreign entity...
- MAPKAPK2-mediated LSP1 phosphorylation and FMLP-induced neutrophil polarizationYue Wu
Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA
Biochem Biophys Res Commun 358:170-5. 2007In neutrophils, the major substrate of MAPKAPK2 (MK2) is an F-actin binding protein LSP1...
- Neutrophil function is preserved in a pooled granulocyte component prepared from whole blood donationsSaber Bashir
NHS Blood and Transplant, Brentwood, UK
Br J Haematol 140:701-11. 2008..The PGC contained similar numbers of neutrophils (approximately 0...
- Activation of the A(3) adenosine receptor suppresses superoxide production and chemotaxis of mouse bone marrow neutrophilsDharini van der Hoeven
Department of Pharmacology and Cardiovascular Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Mol Pharmacol 74:685-96. 2008..Here, we report that the A(3)AR is highly expressed in murine neutrophils isolated from bone marrow...
- Distinct reconstitution of neutrophil functions after allogeneic peripheral blood stem cell transplantationS Scholl
Department of Internal Medicine II Oncology and Hematology, Friedrich Schiller University, Erlanger Allee 101, 07740 Jena, Germany
J Cancer Res Clin Oncol 133:411-5. 2007..The study investigated in detail neutrophil functions shortly after allogeneic peripheral blood stem cell transplantation (PBSCT)...
- Herpes virus entry mediator synergizes with Toll-like receptor mediated neutrophil inflammatory responsesPhilipp Haselmayer
Institute of Immunology, University of Mainz, Mainz, Germany
Immunology 119:404-11. 2006In microbial infections polymorphnuclear neutrophils (PMN) constitute a major part of the innate host defence, based upon their ability to rapidly accumulate in inflamed tissues and clear the site of infection from microbial pathogens by ..
- Modulation of cell adhesion and motility in the immune system by Myo1fSangwon V Kim
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
Science 314:136-9. 2006..In vivo, Myo1f-deficient mice showed increased susceptibility to infection by Listeria monocytogenes and an impaired neutrophil response. Thus, Myo1f directs immune cell motility and innate host defense against infection...
- Polymorphonuclear leukocyte dysfunction syndrome in patients with increasing sepsis severityInes Kaufmann
Department of Anaesthesiology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany
Shock 26:254-61. 2006....
- The Src family kinases Hck and Fgr are dispensable for inside-out, chemoattractant-induced signaling regulating beta 2 integrin affinity and valency in neutrophils, but are required for beta 2 integrin-mediated outside-in signaling involved in sustained aCinzia Giagulli
Department of Pathology, Section of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy
J Immunol 177:604-11. 2006..Addressing inside-out and outside-in signaling in hck(-/-)fgr(-/-) neutrophils, we found that Hck and Fgr do not regulate chemoattractant-induced activation of beta(2) integrin affinity...
- Anti-myeloperoxidase antibodies enhance phagocytosis, IL-8 production, and glucose uptake of polymorphonuclear neutrophils rather than anti-proteinase 3 antibodies leading to activation-induced cell death of the neutrophilsS C Hsieh
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, 7 Chung Shan South Road, Taipei, Taiwan
Clin Rheumatol 26:216-24. 2007..ANCA-activated PMN is not only responsible for the amplified inflammatory process in blood vessel but also initiates immune circuit via triggered macrophage/monocyte by apoptotic PMN through the mechanism of AICD elicited by ANCA...
- Identification of formyl peptides from Listeria monocytogenes and Staphylococcus aureus as potent chemoattractants for mouse neutrophilsErica L Southgate
Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA
J Immunol 181:1429-37. 2008..Consistent with this, fMLF induces bactericidal functions in human neutrophils at nanomolar concentrations...
- Tumor necrosis factor-alpha (TNF-alpha) induces integrin CD11b/CD18 (Mac-1) up-regulation and migration to the CC chemokine CCL3 (MIP-1alpha) on human neutrophils through defined signalling pathwaysFabrizio Montecucco
Laboratory of Phagocyte Physiopathology, First Clinic of Internal Medicine, Department of Internal Medicine and Medical Specialties, University of Genoa Medical School, Genoa, Italy
Cell Signal 20:557-68. 2008Strong evidence suggests that neutrophils may play an active role in acute and chronic inflammatory disorders, such as rheumatoid arthritis and atherosclerosis...
- Rac GTPase isoform-specific regulation of NADPH oxidase and chemotaxis in murine neutrophils in vivo. Role of the C-terminal polybasic domainAkira Yamauchi
Herman B Wells Center for Pediatric Research, the Department of Pediatrics Hematology Oncology, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
J Biol Chem 280:953-64. 2005..To examine whether functional defects in rac2(-/-) neutrophils reflect effects of an overall decrease in total cellular Rac or an isoform-specific role for Rac2, retroviral ..
- Molecular pathways of monocyte emigration into the alveolar air space of intact miceUlrich Maus
Departments of Internal Medicine and Pathology, Justus Liebig University, Giessen, Germany
Am J Respir Crit Care Med 165:95-100. 2002..allowed the separation and quantification of freshly recruited monocytes, resident alveolar macrophages (rAM), neutrophils, and lymphocytes in the bronchoalveolar compartment by fluorescence activated cell sorting technology...
- Effect of serum amyloid A on selected in vitro functions of isolated human neutrophilsM E Gatt
Hematology Unit, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel
J Lab Clin Med 132:414-20. 1998..We evaluated the effects of SAA on human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine (fMLP) in vitro...
- Roles of neutrophil beta 2 integrins in kinetics of bacteremia, extravasation, and tick acquisition of Anaplasma phagocytophila in miceDori L Borjesson
Center for Comparative Medicine, Schools of Medicine Veterinary Medicine, University of California, Davis 95616, USA
Blood 101:3257-64. 2003..A marked increase in the rate of A phagocytophila infection of neutrophils and pathogen burden in blood followed tick feeding...
- Neutrophils deficient in PU.1 do not terminally differentiate or become functionally competentK L Anderson
The Burnham Institute and the Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA
Blood 92:1576-85. 1998..We have also shown that PU.1-null (deficient) neutrophils have neutrophil morphology and express neutrophil-specific markers such as Gr-1 and chloroacetate esterase both ..
- Intracellular calcium waves accompany neutrophil polarization, formylmethionylleucylphenylalanine stimulation, and phagocytosis: a high speed microscopy studyAndrei L Kindzelskii
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA
J Immunol 170:64-72. 2003..Polarized neutrophils exhibited a counterclockwise rotating ryanodine-sensitive juxtamembrane Ca2+ wave during temporal calcium ..
- Increased production of leukocyte microparticles with enhanced expression of adhesion molecules from activated polymorphonuclear leukocytes in severely injured patientsSatoshi Fujimi
Department of Traumatology, Osaka University Medical School, 2 15 Yamadaoka, Suita City, Osaka 565 0871, Japan
J Trauma 54:114-9; discussion 119-20. 2003..The objectives of the present study were to evaluate the production of MPs in severely injured patients and to clarify the role of these MPs...
- The mitochondrial network of human neutrophils: role in chemotaxis, phagocytosis, respiratory burst activation, and commitment to apoptosisGianluca Fossati
Department of Medicine, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK
J Immunol 170:1964-72. 2003It is commonly assumed that human neutrophils possess few, if any, functional mitochondria and that they do not depend on these organelles for cell function...
- Gender dimorphism in neutrophil priming and activation following trauma-hemorrhagic shockBalazs Toth
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Int J Mol Med 11:357-64. 2003..Thus, decreased PMN priming and activation in proestrus females, compared to males, occurs following T-H resulting in decreased cellular injury and organ damage that is likely to contribute to improved outcome under those conditions...
- Effect of interleukin-8 and granulocyte colony-stimulating factor on priming and activation of bovine neutrophilsGordon B Mitchell
Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada N1G 2W1
Infect Immun 71:1643-9. 2003b>Neutrophils are important effector cells in innate and acquired immunity, but the magnitude and character of their phagocytic and bactericidal responses depend on cues derived from mediators in the local microenvironment...
- Effect of butylated hydroxyanisole and some of its derivatives on human neutrophil oxidative burst: chemiluminescence evaluationPier Carlo Braga
Department of Pharmacology, School of Medicine, University of Milan, Italy
Pharmacology 68:9-16. 2003..response begins during the reperfusion phase following an ischemic insult in which polymorphonuclear neutrophils (PMNs) play an important role and the release of reactive oxygen species (ROS) causes further damage and a ..
- Evidence for antibody-catalyzed ozone formation in bacterial killing and inflammationPaul Wentworth
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Science 298:2195-9. 2002..This species is also generated during the oxidative burst of activated human neutrophils and during inflammation...
- Neutrophil Accumulation in Bacterial PneumoniaSamithamby Jeyaseelan; Fiscal Year: 2009Bacterial pneumonia is a leading cause of death. Recruitment of neutrophils into the lungs is one of the most important defense mechanisms in the initial host defense against bacterial infection...
- HMGB1 and neutrophil efferocytosis.Edward Abraham; Fiscal Year: 2010..In recent studies, we found that HMGB1 inhibits phagocytosis of apoptotic neutrophils by macrophages in vivo and in vitro...
- Neutrophil Accumulation in Bacterial PneumoniaSamithamby Jeyaseelan; Fiscal Year: 2009Bacterial pneumonia is a leading cause of death. Recruitment of neutrophils into the lungs is one of the most important defense mechanisms in the initial host defense against bacterial infection...
- NEUTROPHIL-INDUCED LIVER INJURY TOXICITYHartmut Jaeschke; Fiscal Year: 2005b>Neutrophils can cause impaired liver function, parenchymal injury and even liver failure during a number of important clinical situations including hepatic ischemia-reperfusion, hemorrhagic shock and resuscitation, endotoxemia and sepsis,..
- Oxidant Stress Mechanisms in PreeclampsiaScott W Walsh; Fiscal Year: 2010..b>Neutrophils infiltrating the vasculature could cause inflammation and vasoconstriction by release of toxic compounds, such ..
- Urokinase, Neutrophil Activation and Acute Lung Injury.Edward Abraham; Fiscal Year: 2010..fibrinolytic pathways: 1) by enhancing neutrophil activation and 2) by decreasing phagocytosis and clearance of neutrophils in the lungs...
- Neutrophil Accumulation in Bacterial PneumoniaSamithamby Jeyaseelan; Fiscal Year: 2010Bacterial pneumonia is a leading cause of death. Recruitment of neutrophils into the lungs is one of the most important defense mechanisms in the initial host defense against bacterial infection...
- DEMYELINATING DISEASE: VIRAL AND IMMUNE FUNCTIONStephen Stohlman; Fiscal Year: 2007..Project 12 focuses on the initial events in CNS inflammation including the role of innate cytokines and neutrophils in shaping both the innate and adaptive CNS immune response, and an exciting new approach to understanding how ..
- HMGB1 and neutrophil efferocytosis.Edward Abraham; Fiscal Year: 2009..In recent studies, we found that HMGB1 inhibits phagocytosis of apoptotic neutrophils by macrophages in vivo and in vitro...
- Anaplasma regulation of host granulocyte functionJohn Stephen Dumler; Fiscal Year: 2010..is an emerging tick-borne disease caused by Anaplasma phagocytophilum, an obligate intracellular bacterium of neutrophils. A...
- C3A ACTIVATION OF LEUKOCYTES IN INFLAMMATIONTONY HUGLI; Fiscal Year: 2002..Extensive evidence indicates that neutrophils, monocytes and eosinophils are attracted to sites of inflammation by specific chemotactic factors, including ..
- PHASE 2 & 3 TRIALS OF HIGH-DOSE ORAL N-ACETYLCYSTEINE IN CYSTIC FIBROSISCarol Conrad; Fiscal Year: 2007..Recently, the applicant observed that redox imbalance in CF also occurs intracellularly, in blood neutrophils, featuring low levels of reduced glutathione (GSH)...
- Ras and Chemokine Stimulated Neutrophil PolarizationCindy Knall; Fiscal Year: 2004Polymorphonuclear leukocytes, neutrophils, are the most abundant leukocytes in peripheral blood. They play a major role in innate immunity and may contribute to the development of the adaptive immune response...
- BIOLOGY, IMMUNOLOGY & THERAPY OF ACANTHAMOEBA KERATITISHassan Alizadeh; Fiscal Year: 2009..1) The innate immune system plays an important role in Acanthamoeba keratitis and polymorphonuclear neutrophils (PMN) are the prominent inflammatory cells in Acanthamoeba keratitis lesions; 2) neutrophils are important in ..
- Vascular adhesion protein-1 (VAP-1) as a therapeutic target in strokeDALE ALAN PELLIGRINO; Fiscal Year: 2010..e., neutrophils, monocytes, lymphocytes) in peripheral vascular beds...
- NEUTROPHIL SEQUESTRATION AND EMIGRATION IN THE LUNGCLAIRE DOERSCHUK; Fiscal Year: 2001Neutrophil sequestration and emigration in the lungs take place primarily in the capillaries. Rolling of neutrophils does not occur at this site, because most capillary segments are narrower than neutrophils...
- Mechanisms of neuronal injury during virus infection of the CNSCHARLES LEE HOWE; Fiscal Year: 2010..infection of the CNS using the Theiler's murine encephalomyelitis virus to directly test the role of neutrophils in the initiation of neuronal apoptosis...
- Mechanisms of neuronal injury during virus infection of the CNSCharles Howe; Fiscal Year: 2009..infection of the CNS using the Theiler's murine encephalomyelitis virus to directly test the role of neutrophils in the initiation of neuronal apoptosis...
- NEUTROPHIL ACTIVATION IN ACUTE LUNG INJURYEdward Abraham; Fiscal Year: 2004..IL-1, TNF, and MIP-2, and in activation of the transcriptional regulatory factors NF-kB and CREB in lung neutrophils. After endotoxemia, but not hemorrhage, adrenergic blockade increases expression of proinflammatory cytokines ..
- MNEI/SerpinB1: A modulator of innate pulmonary defenseEILEEN REMOLD O DONNELL; Fiscal Year: 2007..NSPs) (elastase, cathepsin G and proteinase-3) released at inflammatory sites by degranulating or necrotic neutrophils are major contributors to the pathology of cystic fibrosis and chronic obstructive pulmonary disease (COPD)...
- MNEI/SerpinB1: A modulator of innate pulmonary defenseEILEEN REMOLD O DONNELL; Fiscal Year: 2009..NSPs) (elastase, cathepsin G and proteinase-3) released at inflammatory sites by degranulating or necrotic neutrophils are major contributors to the pathology of cystic fibrosis and chronic obstructive pulmonary disease (COPD)...
- Oxidant Stress Mechanisms in PreeclampsiaScott Walsh; Fiscal Year: 2007..The cause of preeclampsia is not known. We propose that increased levels of lipid peroxides (LOOH) activate neutrophils, as well as endothelial and vascular smooth muscle cells, resulting in the elaboration of the neutrophil ..
- Oxidant Stress Mechanisms in PreeclampsiaScott Walsh; Fiscal Year: 2003..The cause of preeclampsia is not known. We propose that increased levels of lipid peroxides (LOOH) activate neutrophils, as well as endothelial and vascular smooth muscle cells, resulting in the elaboration of the neutrophil ..