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      1. Author :
        Pettersson, U. S.; Christoffersson, G.; Massena, S.; Ahl, D.; Jansson, L.; Henriksnas, J.; Phillipson, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        6
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29, Animals; Blood Glucose/metabolism; Cell Adhesion/drug effects; Cell Count; Cell Movement/drug effects; Chemokine CXCL2/pharmacology; Diabetes Mellitus, Type 1/blood/complications/*immunology/microbiology; Diabetes Mellitus, Type 2/blood/complications/*immunology/microbiology; Diet, High-Fat/adverse effects; Disease Models, Animal; Hyperglycemia/chemically induced/complications; Inflammation/blood/complications/immunology/microbiology; Leukocytes/cytology/drug effects/*immunology/microbiology; Male; Mice; Mice, Inbred C57BL; Phagocytes/cytology/drug effects/microbiology; Staphylococcus aureus/physiology
      12. Abstract :
        BACKGROUND: Patients suffering from diabetes show defective bacterial clearance. This study investigates the effects of elevated plasma glucose levels during diabetes on leukocyte recruitment and function in established models of inflammation. METHODOLOGY/PRINCIPAL FINDINGS: Diabetes was induced in C57Bl/6 mice by intravenous alloxan (causing severe hyperglycemia), or by high fat diet (moderate hyperglycemia). Leukocyte recruitment was studied in anaesthetized mice using intravital microscopy of exposed cremaster muscles, where numbers of rolling, adherent and emigrated leukocytes were quantified before and during exposure to the inflammatory chemokine MIP-2 (0.5 nM). During basal conditions, prior to addition of chemokine, the adherent and emigrated leukocytes were increased in both alloxan- (62+/-18% and 85+/-21%, respectively) and high fat diet-induced (77+/-25% and 86+/-17%, respectively) diabetes compared to control mice. MIP-2 induced leukocyte emigration in all groups, albeit significantly more cells emigrated in alloxan-treated mice (15.3+/-1.0) compared to control (8.0+/-1.1) mice. Bacterial clearance was followed for 10 days after subcutaneous injection of bioluminescent S. aureus using non-invasive IVIS imaging, and the inflammatory response was assessed by Myeloperoxidase-ELISA and confocal imaging. The phagocytic ability of leukocytes was assessed using LPS-coated fluorescent beads and flow cytometry. Despite efficient leukocyte recruitment, alloxan-treated mice demonstrated an impaired ability to clear bacterial infection, which we found correlated to a 50% decreased phagocytic ability of leukocytes in diabetic mice. CONCLUSIONS/SIGNIFICANCE: These results indicate that reduced ability to clear bacterial infections observed during experimentally induced diabetes is not due to reduced leukocyte recruitment since sustained hyperglycemia results in increased levels of adherent and emigrated leukocytes in mouse models of type 1 and type 2 diabetes. Instead, decreased phagocytic ability observed for leukocytes isolated from diabetic mice might account for the impaired bacterial clearance.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21799868
      14. Call Number :
        PKI @ kd.modi @ 20
      15. Serial :
        10455
      1. Author :
        Close, P.; Gillard, M.; Ladang, A.; Jiang, Z.; Papuga, J.; Hawkes, N.; Nguyen, L.; Chapelle, J. P.; Bouillenne, F.; Svejstrup, J.; Fillet, M.; Chariot, A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Biol Chem
      6. Products :
      7. Volume :
        287
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, Carrier Proteins/genetics/*metabolism; Cell Line, Tumor; *Cell Movement; Gene Deletion; HEK293 Cells; Humans; Melanoma/genetics/*metabolism/pathology; Multiprotein Complexes/genetics/*metabolism; Neoplasm Invasiveness; Neoplasm Proteins/genetics/*metabolism; Proteins/genetics/*metabolism; RNA Polymerase II/genetics/metabolism
      12. Abstract :
        The Elongator complex is composed of 6 subunits (Elp1-Elp6) and promotes RNAPII transcript elongation through histone acetylation in the nucleus as well as tRNA modification in the cytoplasm. This acetyltransferase complex directly or indirectly regulates numerous biological processes ranging from exocytosis and resistance to heat shock in yeast to cell migration and neuronal differentiation in higher eukaryotes. The identity of human ELP1 through ELP4 has been reported but human ELP5 and ELP6 have remained uncharacterized. Here, we report that DERP6 (ELP5) and C3ORF75 (ELP6) encode these subunits of human Elongator. We further investigated the importance and function of these two subunits by a combination of biochemical analysis and cellular assays. Our results show that DERP6/ELP5 is required for the integrity of Elongator and directly connects ELP3 to ELP4. Importantly, the migration and tumorigenicity of melanoma-derived cells are significantly decreased upon Elongator depletion through ELP1 or ELP3. Strikingly, DERP6/ELP5 and C3ORF75/ELP6-depleted melanoma cells have similar defects, further supporting the idea that DERP6/ELP5 and C3ORF75/ELP6 are essential for Elongator function. Together, our data identify DERP6/ELP5 and C3ORF75/ELP6 as key players for migration, invasion and tumorigenicity of melanoma cells, as integral subunits of Elongator.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22854966
      14. Call Number :
        PKI @ kd.modi @ 20
      15. Serial :
        10530
      1. Author :
        Nahrendorf, M.; Keliher, E.; Marinelli, B.; Waterman, P.; Feruglio, P. F.; Fexon, L.; Pivovarov, M.; Swirski, F. K.; Pittet, M. J.; Vinegoni, C.; Weissleder, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Proc Natl Acad Sci U S A
      6. Products :
      7. Volume :
        107
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Flow Cytometry; Fluorescent Dyes/*diagnostic use; Image Processing, Computer-Assisted/methods; Mice; Mice, Inbred C57BL; Nanoparticles/*diagnostic use; Neoplasms/*diagnosis; Positron-Emission Tomography/*methods; Tomography, X-Ray Computed/*methods
      12. Abstract :
        Fusion imaging of radionuclide-based molecular (PET) and structural data [x-ray computed tomography (CT)] has been firmly established. Here we show that optical measurements [fluorescence-mediated tomography (FMT)] show exquisite congruence to radionuclide measurements and that information can be seamlessly integrated and visualized. Using biocompatible nanoparticles as a generic platform (containing a (18)F isotope and a far red fluorochrome), we show good correlations between FMT and PET in probe concentration (r(2) > 0.99) and spatial signal distribution (r(2) > 0.85). Using a mouse model of cancer and different imaging probes to measure tumoral proteases, macrophage content and integrin expression simultaneously, we demonstrate the distinct tumoral locations of probes in multiple channels in vivo. The findings also suggest that FMT can serve as a surrogate modality for the screening and development of radionuclide-based imaging agents.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20385821
      14. Call Number :
        PKI @ kd.modi @ 21
      15. Serial :
        10375
      1. Author :
        Hutteman, M.; Mieog, J. S.; van der Vorst, J. R.; Dijkstra, J.; Kuppen, P. J.; van der Laan, A. M.; Tanke, H. J.; Kaijzel, E. L.; Que, I.; van de Velde, C. J.; Lowik, C. W.; Vahrmeijer, A. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Surg Oncol
      6. Products :
      7. Volume :
        37
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Colorectal Neoplasms/*metabolism/*secondary; Disease Models, Animal; Image Processing, Computer-Assisted; Integrin alphaVbeta3/*metabolism; Intraoperative Period; Liver Neoplasms/*pathology; Male; Neoplasm Transplantation; Rats; Spectroscopy, Near-Infrared/*methods; Tumor Cells, Cultured
      12. Abstract :
        AIM: Near-infrared (NIR) fluorescence optical imaging is a promising technique to assess the extent of colorectal metastases during curative-intended surgery. However, NIR fluorescence imaging of liver metastases is highly challenging due to hepatic uptake and clearance of many fluorescent dyes. In the current study, the biodistribution and the ability to demarcate liver and peritoneal metastases were assessed during surgery in a syngeneic rat model of colorectal cancer using an integrin alpha(v)beta(3)-directed NIR fluorescence probe. METHODS: Liver tumors and peritoneal metastases were induced in 7 male WAG/Rij rats by subcapsular inoculation of 0.5 x 10(6) CC531 colorectal cancer rat cells into three distinct liver lobes. Intraoperative and ex vivo fluorescence measurements were performed 24 (N = 3 rats, 7 tumors) and 48 h (N = 4 rats, 9 tumors) after intravenous administration of the integrin alpha(v)beta(3)-directed NIR fluorescence probe. RESULTS: Colorectal metastases had a minimal two-fold higher NIR fluorescence signal than healthy liver tissue and other abdominal organs (p < 0.001). The tumor-to-background ratio was independent of time of imaging (24 h vs. 48 h post-injection; p = 0.31), which facilitates flexible operation planning in future clinical applications. Total fluorescence intensity was significantly correlated with the size of metastases (R(2) = 0.92 for the 24 h group, R(2) = 0.96 for the 48 h group). CONCLUSION: These results demonstrate that colorectal intra-abdominal metastases can be clearly demarcated during surgery using an integrin alpha(v)beta(3) targeting NIR fluorescence probe. Translating these findings to the clinic will have an excellent potential to substantially improve the quality of cancer surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21215590
      14. Call Number :
        PKI @ kd.modi @ 23
      15. Serial :
        10366
      1. Author :
        Zhang, X.; Bloch, S.; Akers, W.; Achilefu, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Curr Protoc Cytom
      6. Products :
      7. Volume :
        Chapter 12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Cell Line, Tumor; Diagnostic Imaging/*methods; Fluorescent Dyes/chemistry/metabolism; Humans; Mice; Molecular Probes/*diagnostic use; Nanoparticles/chemistry; Quantum Dots; Spectroscopy, Near-Infrared/*methods
      12. Abstract :
        Cellular and tissue imaging in the near-infrared (NIR) wavelengths between 700 and 900 nm is advantageous for in vivo imaging because of the low absorption of biological molecules in this region. This unit presents protocols for small animal imaging using planar and fluorescence lifetime imaging techniques. Included is an overview of NIR fluorescence imaging of cells and small animals using NIR organic fluorophores, nanoparticles, and multimodal imaging probes. The development, advantages, and application of NIR fluorescent probes that have been used for in vivo imaging are also summarized. The use of NIR agents in conjunction with visible dyes and considerations in selecting imaging agents are discussed. We conclude with practical considerations for the use of these dyes in cell and small animal imaging applications.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22470154
      14. Call Number :
        PKI @ kd.modi @ 24
      15. Serial :
        10386
      1. Author :
        Leuschner, F.; Rauch, P. J.; Ueno, T.; Gorbatov, R.; Marinelli, B.; Lee, W. W.; Dutta, P.; Wei, Y.; Robbins, C.; Iwamoto, Y.; Sena, B.; Chudnovskiy, A.; Panizzi, P.; Keliher, E.; Higgins, J. M.; Libby, P.; Moskowitz, M. A.; Pittet, M. J.; Swirski, F. K.; Weissleder, R.; Nahrendorf, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Exp Med
      6. Products :
      7. Volume :
        209
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Adoptive Transfer; Animals; Biological Markers/metabolism; Cell Death/genetics; Disease Models, Animal; Female; *Hematopoiesis, Extramedullary; Inflammation/immunology/metabolism; Interleukin-1beta/genetics/metabolism; Kinetics; Macrophages/cytology/*physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Monocytes/*cytology/*physiology; Myeloid Cells/metabolism; Myocardial Infarction/immunology/pathology/*physiopathology; Signal Transduction; Spleen/physiology; Stroke/immunology/metabolism; Wound Healing/physiology
      12. Abstract :
        Monocytes (Mo) and macrophages (MPhi) are emerging therapeutic targets in malignant, cardiovascular, and autoimmune disorders. Targeting of Mo/MPhi and their effector functions without compromising innate immunity's critical defense mechanisms first requires addressing gaps in knowledge about the life cycle of these cells. Here we studied the source, tissue kinetics, and clearance of Mo/MPhi in murine myocardial infarction, a model of acute inflammation after ischemic injury. We found that a) Mo tissue residence time was surprisingly short (20 h); b) Mo recruitment rates were consistently high even days after initiation of inflammation; c) the sustained need of newly made Mo was fostered by extramedullary monocytopoiesis in the spleen; d) splenic monocytopoiesis was regulated by IL-1beta; and e) the balance of cell recruitment and local death shifted during resolution of inflammation. Depending on the experimental approach, we measured a 24 h Mo/MPhi exit rate from infarct tissue between 5 and 13% of the tissue cell population. Exited cells were most numerous in the blood, liver, and spleen. Abrogation of extramedullary monocytopoiesis proved deleterious for infarct healing and accelerated the evolution of heart failure. We also detected rapid Mo kinetics in mice with stroke. These findings expand our knowledge of Mo/MPhi flux in acute inflammation and provide the groundwork for novel anti-inflammatory strategies for treating heart failure.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22213805
      14. Call Number :
        PKI @ kd.modi @ 27
      15. Serial :
        10370
      1. Author :
        Keereweer, S.; Mol, I. M.; Kerrebijn, J. D.; Van Driel, P. B.; Xie, B.; Baatenburg de Jong, R. J.; Vahrmeijer, A. L.; Lowik, C. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Surg Oncol
      6. Products :
      7. Volume :
        105
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Carcinoma, Squamous Cell/*pathology/surgery; Fluorescent Dyes/*diagnostic use; Humans; Integrin alphaVbeta3/*metabolism; Mice; Mice, Inbred BALB C; Mouth Neoplasms/*pathology/surgery; Spectroscopy, Near-Infrared; *Surgery, Computer-Assisted
      12. Abstract :
        BACKGROUND AND OBJECTIVES: Near-infrared (NIR) fluorescence optical imaging is a promising technique to assess the tumor margins during cancer surgery. This technique requires targeting by specific fluorescence agents to differentiate tumor from normal surrounding tissue. We assessed the feasibility of cancer detection using NIR fluorescence agents that target either alphavbeta3 integrins or the enhanced permeability and retention (EPR) effect in an orthotopic mouse model of oral cancer. METHODS: Binding of the integrin-targeted agent to tumor cells was assessed in vitro. Oral cancer was induced in 6 BALB/c nu/nu mice by submucosal inoculation of human OSC19-luc cells into the tongue. Tumor growth was followed with bioluminescence imaging. A combination of agents targeting integrins or EPR effect was injected followed by fluorescence imaging in vivo and ex vivo after resection of the tongues. RESULTS: Oral cancer was clearly demarcated in vitro; in vivo; and on histological analysis with sufficient tumor-to-background ratios of the contrast agents. CONCLUSION: This study demonstrates the feasibility of optical imaging of oral squamous cell carcinoma based on targeting of alphavbeta3 integrins and the EPR effect. Once these NIR fluorescence agents become available for clinical testing, optical image-guided surgery could reduce residual disease after oral cancer surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21952950
      14. Call Number :
        PKI @ kd.modi @ 28
      15. Serial :
        10368
      1. Author :
        Ale, A.; Ermolayev, V.; Herzog, E.; Cohrs, C.; de Angelis, M. H.; Ntziachristos, V.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Methods
      6. Products :
      7. Volume :
        9
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bone Remodeling; Disease Models, Animal; Equipment Design; Female; Fluorescence; Head and Neck Neoplasms/pathology/radiography; Image Processing, Computer-Assisted/*methods; Lung Neoplasms/pathology/radiography; Mammary Neoplasms, Experimental/pathology/radiography; Mice; Osteogenesis Imperfecta/pathology/radiography; Tomography, Optical/*methods; Tomography, X-Ray Computed/*methods
      12. Abstract :
        The development of hybrid optical tomography methods to improve imaging performance has been suggested over a decade ago and has been experimentally demonstrated in animals and humans. Here we examined in vivo performance of a camera-based hybrid fluorescence molecular tomography (FMT) system for 360 degrees imaging combined with X-ray computed tomography (XCT). Offering an accurately co-registered, information-rich hybrid data set, FMT-XCT has new imaging possibilities compared to stand-alone FMT and XCT. We applied FMT-XCT to a subcutaneous 4T1 tumor mouse model, an Aga2 osteogenesis imperfecta model and a Kras lung cancer mouse model, using XCT information during FMT inversion. We validated in vivo imaging results against post-mortem planar fluorescence images of cryoslices and histology data. Besides offering concurrent anatomical and functional information, FMT-XCT resulted in the most accurate FMT performance to date. These findings indicate that addition of FMT optics into the XCT gantry may be a potent upgrade for small-animal XCT systems.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22561987
      14. Call Number :
        PKI @ kd.modi @ 29
      15. Serial :
        10363
      1. Author :
        Leszczynska, K.; Namiot, A.; Cruz, K.; Byfield, F. J.; Won, E.; Mendez, G.; Sokolowski, W.; Savage, P. B.; Bucki, R.; Janmey, P. A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Appl Microbiol
      6. Products :
      7. Volume :
        110
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen 5, Pseudomonas aeruginosa Xen 5, Anti-Bacterial Agents/administration & dosage/*pharmacology/therapeutic; use; Antimicrobial Cationic Peptides/chemistry; Biofilms/drug effects; Cholic Acid/chemistry; Cystic Fibrosis/microbiology; Hemolysis/drug effects; Humans; *Poloxamer; Pseudomonas Infections/drug therapy; Pseudomonas aeruginosa/drug effects/growth & development; Skin Diseases, Bacterial/drug therapy; Staphylococcus aureus/drug effects; Steroids/administration & dosage/*pharmacology/therapeutic use; *Surface-Active Agents
      12. Abstract :
        AIMS: Ceragenin CSA-13 is a synthetic mimic of cationic antibacterial peptides, with facial amphiphilic morphology reproduced using a cholic acid scaffold. Previous data have shown that this molecule displays broad-spectrum antibacterial activity, which decreases in the presence of blood plasma. However, at higher concentrations, CSA-13 can cause lysis of erythrocytes. This study was designed to assess in vitro antibacterial and haemolytic activity of CSA-13 in the presence of pluronic F-127. METHODS AND RESULTS: CSA-13 bactericidal activity against clinical strains of bacteria associated with topical infections and in an experimental setting relevant to their pathophysiological environment, such as various epithelial tissue fluids and the airway sputum of patients suffering from cystic fibrosis (CF), was evaluated using minimum inhibitory and minimum bactericidal concentration (MIC/MBC) measurements and bacterial killing assays. We found that in the presence of pluronic F-127, CSA-13 antibacterial activity was only slightly decreased, but CSA-13 haemolytic activity was significantly inhibited. CSA-13 exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, including methicillin-resistant strains, Pseudomonas aeruginosa present in CF sputa, and biofilms formed by different Gram (+) and Gram (-) bacteria. CSA-13 bactericidal action is partially compromised in the presence of plasma, but is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid. The synergistic action of CSA-13, determined by the use of a standard checkerboard assay, reveals an increase in CSA-13 antibacterial activity in the presence of host defence molecules such as the cathelicidin LL-37 peptide, lysozyme, lactoferrin and secretory phospholipase A (sPLA). CONCLUSION: These results suggest that CSA-13 may be useful to prevent and treat topical infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Combined application of CSA-13 with pluronic F-127 may be beneficial by reducing CSA-13 toxicity.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20961363
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10389
      1. Author :
        Yan, J.; Meng, X.; Wancket, L. M.; Lintner, K.; Nelin, L. D.; Chen, B.; Francis, K. P.; Smith, C. V.; Rogers, L. K.; Liu, Y.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Immunol
      6. Products :
      7. Volume :
        188
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Escherichia coli/immunology; Escherichia coli Infections/enzymology/immunology/*prevention & control; Extracellular Space/genetics/*immunology/metabolism; Glutathione Reductase/deficiency/genetics/*physiology; Humans; Mice; Mice, Inbred C3H; Mice, Knockout; Neutrophils/*immunology/*metabolism/microbiology; Oxidative Stress/genetics/*immunology; Phagocytosis/genetics/*immunology; Staphylococcal Infections/enzymology/immunology/*prevention & control; Staphylococcus aureus/immunology
      12. Abstract :
        Glutathione reductase (Gsr) catalyzes the reduction of glutathione disulfide to glutathione, which plays an important role in the bactericidal function of phagocytes. Because Gsr has been implicated in the oxidative burst in human neutrophils and is abundantly expressed in the lymphoid system, we hypothesized that Gsr-deficient mice would exhibit marked defects during the immune response against bacterial challenge. We report in this study that Gsr-null mice exhibited enhanced susceptibility to Escherichia coli challenge, indicated by dramatically increased bacterial burden, cytokine storm, striking histological abnormalities, and substantially elevated mortality. Additionally, Gsr-null mice exhibited elevated sensitivity to Staphylococcus aureus. Examination of the bactericidal functions of the neutrophils from Gsr-deficient mice in vitro revealed impaired phagocytosis and defective bacterial killing activities. Although Gsr catalyzes the regeneration of glutathione, a major cellular antioxidant, Gsr-deficient neutrophils paradoxically produced far less reactive oxygen species upon activation both ex vivo and in vivo. Unlike wild-type neutrophils that exhibited a sustained oxidative burst upon stimulation with phorbol ester and fMLP, Gsr-deficient neutrophils displayed a very transient oxidative burst that abruptly ceased shortly after stimulation. Likewise, Gsr-deficient neutrophils also exhibited an attenuated oxidative burst upon encountering E. coli. Biochemical analysis revealed that the hexose monophosphate shunt was compromised in Gsr-deficient neutrophils. Moreover, Gsr-deficient neutrophils displayed a marked impairment in the formation of neutrophil extracellular traps, a bactericidal mechanism that operates after neutrophil death. Thus, Gsr-mediated redox regulation is crucial for bacterial clearance during host defense against massive bacterial challenge.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22279102
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10398
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