13 results on '"RAPID MOBILIZATION"'
Search Results
2. Effect of the CXCR4 antagonist plerixafor on endogenous neutrophil dynamics in the bone marrow, lung and spleen
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Janesh Pillay, Leo M. Carlin, Sara M. Rankin, David C. A. Gaboriau, Chiara Pirillo, Nicola Tregay, Edwin R. Chilvers, Charlotte Summers, Goda Juzenaite, Neda Farahi, Cristina Lo Celso, Katia De Filippo, Summers, Charlotte [0000-0002-7269-2873], Apollo - University of Cambridge Repository, and Wellcome Trust
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0301 basic medicine ,Pathology ,Benzylamines ,Neutrophils ,Inbred C57BL ,0601 Biochemistry and Cell Biology ,Cyclams ,MYELOKATHEXIS ,Mice ,Leukocyte Count ,0302 clinical medicine ,Spleen/cytology ,Bone Marrow ,Heterocyclic Compounds ,Pulmonary fibrosis ,Immunology and Allergy ,Heterocyclic Compounds/pharmacology ,Lung ,Hematology ,CXCR4 antagonist ,RAPID MOBILIZATION ,Neutrophils/cytology ,Technetium ,Hematopoietic Stem Cell Mobilization ,Radiopharmaceuticals/administration & dosage ,medicine.anatomical_structure ,1107 Immunology ,Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ,Cell Tracking ,030220 oncology & carcinogenesis ,Bone Marrow/diagnostic imaging ,CHEMOKINE RECEPTOR ,Hematopoietic Stem Cell Mobilization/methods ,Female ,WHIM-SYNDROME ,Life Sciences & Biomedicine ,WHIM syndrome ,medicine.drug ,RECRUITMENT ,medicine.medical_specialty ,neutrophil activation ,Single Photon Emission Computed Tomography Computed Tomography ,Immunology ,INHIBITION ,neutrophil dynamics ,Cell Tracking/methods ,Biology ,AMD3100 ,03 medical and health sciences ,Lung/cytology ,neutrophil mobilization ,Internal medicine ,medicine ,Animals ,Humans ,Myelokathexis ,RELEASE ,Science & Technology ,Hematopoietic Stem Cells/cytology ,Plerixafor ,PLATFORM ,Granulocyte-Macrophage Colony-Stimulating Factor ,Cell Biology ,medicine.disease ,Hematopoietic Stem Cells ,Mice, Inbred C57BL ,030104 developmental biology ,CELLS ,Bone marrow ,Radiopharmaceuticals ,Technetium/administration & dosage ,Spleen - Abstract
Treatment with the CXCR4 antagonist, plerixafor (AMD3100), has been proposed for clinical use in patients with WHIM (warts, hypogammaglobulinemia, infections and myelokathexis) syndrome and in pulmonary fibrosis. However, there is controversy with respect to the impact of plerixafor on neutrophil dynamics in the lung, which may affect its safety profile. In this study we investigated the kinetics of endogenous neutrophils by direct imaging, using confocal intravital microscopy in mouse bone marrow, spleen and lungs. Neutrophils are observed increasing their velocity and exiting the bone marrow following plerixafor administration, with a concomitant increase in neutrophil numbers in the blood and spleen, while the marginated pool of neutrophils in the lung microvasculature remained unchanged in terms of numbers and cell velocity. Use of autologous radiolabeled neutrophils and SPECT/CT imaging in healthy volunteers showed that plerixafor did not affect GM-CSF-primed neutrophil entrapment or release in the lungs. Taken together these data suggest that plerixafor causes neutrophil mobilization from the bone marrow but does not impact on lung marginated neutrophil dynamics and thus is unlikely to compromise respiratory host defense both in humans and mice., This work was funded by a grant provided to JP by the Lung Foundation Netherlands (5.2.14.058JO), the NIHR Cambridge Biomedical Research Centre and NIHR Imperial Biomedical Research Centre. ERC and CS’ laboratories receive grant support from the Medical Research Council, Wellcome Trust, NIHR, GlaxoSmithKline, MedImmune Ltd., and Bristol-Myers Squibb. CLC is supported by Bloodwise (12033), CRUK (C36195/A1183) and European Research Council (ERC) (337066). CP is supported by Bloodwise (12033). The Facility for Imaging by Light Microscopy (FILM) at Imperial College London is part-supported by funding from the Wellcome Trust (grant 104931/Z/14/Z) and BBSRC (grant BB/L015129/1). KDF is supported by funding from the Wellcome Trust (201356/Z/16/Z). LMC is supported by core funding from Cancer Research UK (A23983 and A17196).
- Published
- 2020
3. Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells.
- Author
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Dar, A., Schajnovitz, A., Lapid, K., Kalinkovich, A., Itkin, T., Ludin, A., Kao, W.-M., Battista, M., Tesio, M., Kollet, O., Cohen, N. N., Margalit, R., Buss, E. C., Baleux, F., Oishi, S., Fujii, N., Larochelle, A., Dunbar, C. E., Broxmeyer, H. E., and Frenette, P. S.
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CHEMOKINES , *LEUCOCYTES , *STEM cell transplantation , *HEMATOPOIETIC stem cells , *POLYSACCHARIDES , *NORADRENALINE , *CELL receptors , *ANIMAL experimentation , *BIOTHERAPY , *BONE marrow , *CELL culture , *COMPARATIVE studies , *CONNECTIVE tissue cells , *CYTOKINES , *HETEROCYCLIC compounds , *RESEARCH methodology , *MEDICAL cooperation , *MICE , *RESEARCH , *EVALUATION research , *PHARMACODYNAMICS , *CELL physiology - Abstract
Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine stromal cell derived factor-1 (SDF-1) to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes. Intra-bone injection of biotinylated SDF-1 also enhanced release of this chemokine and murine progenitor cell mobilization. AMD3100 directly induced SDF-1 release from CXCR4(+) human bone marrow osteoblasts and endothelial cells and activated uPA in a CXCR4/JNK-dependent manner. Additionally, ROS inhibition reduced AMD3100-induced SDF-1 release, activation of circulating uPA and mobilization of progenitor cells. Norepinephrine treatment, mimicking acute stress, rapidly increased SDF-1 release and progenitor cell mobilization, whereas β2-adrenergic antagonist inhibited both steady state and AMD3100-induced SDF-1 release and progenitor cell mobilization in mice. In conclusion, this study reveals that SDF-1 release from bone marrow stromal cells to the circulation emerges as a pivotal mechanism essential for steady-state egress and rapid mobilization of hematopoietic progenitor cells, but not mature leukocytes. [ABSTRACT FROM AUTHOR]
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- 2011
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4. Two distinct CXCR4 antagonists mobilize progenitor cells in mice by different mechanisms
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Andia N. Redpath, Suet-Ping Wong, Sara M. Rankin, Moïra François, Dominique Bonnet, Laboratoire d'Innovation Thérapeutique (LIT), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)
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0301 basic medicine ,Chemokine ,Hematopoiesis and Stem Cells ,BONE-MARROW ,PROMOTING MIGRATION ,[SDV]Life Sciences [q-bio] ,G-CSF ,Pharmacology ,CXCR4 ,MESENCHYMAL STEM-CELLS ,03 medical and health sciences ,Chemokine receptor ,NOD/SCID MICE ,[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,medicine ,Stromal cell-derived factor 1 ,Progenitor cell ,ComputingMilieux_MISCELLANEOUS ,Science & Technology ,CXCR4 antagonist ,biology ,MARROW STROMAL CELLS ,RAPID MOBILIZATION ,Mesenchymal stem cell ,Hematology ,3. Good health ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,HEMATOPOIETIC STEM ,HUMAN-IMMUNODEFICIENCY-VIRUS ,CHEMOKINE RECEPTOR ,embryonic structures ,biology.protein ,Bone marrow ,Life Sciences & Biomedicine - Abstract
Pharmacological mobilization of hematopoietic progenitor cells (HPCs) is used clinically to harvest HPCs for bone marrow transplants. It is now widely accepted that the CXCR4:CXCL12 chemokine axis plays a critical role in the retention of HPCs in the bone marrow, and CXCR4 antagonists have been developed for their mobilization. The first of this class of drugs to be US Food and Drug Administration-approved was the bicyclam AMD3100. In addition to mobilizing HPCs and leukocytes in naïve mice, AMD3100 has been shown to mobilize mesenchymal progenitor cells (MPCs) in vascular endothelial growth factor (VEGF-A) pretreated mice. AMD3100 binds to the transmembrane region of CXCR4 and is thought to mobilize HPCs by reversing the gradient of CXCL12 across the bone marrow endothelium. Consistent with this hypothesis, our data show that selective neutralization of CXCL12, with chalcone 4-phosphate (C4P), inhibited AMD3100-stimulated mobilization of HPCs and leukocytes in naïve mice and MPCs in VEGF-A pretreated mice. In contrast it is shown here that the CXCR4 antagonist KRH3955 that binds to the extracellular loop of CXCR4 does not reverse the CXCL12 chemokine gradient. However, this drug efficiently mobilizes HPCs, a response that is not inhibited by C4P. In contrast, KRH3955 does not mobilize MPCs in VEGF-A pretreated mice. These data suggest that CXCR4 antagonists that bind to distinct regions of the receptor mobilize progenitor cells by distinct molecular mechanisms.
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- 2017
5. CXCR4, the master regulator of neutrophil trafficking in homoeostasis and disease
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Sara M. Rankin, Katia De Filippo, and Wellcome Trust
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0301 basic medicine ,Chemokine ,Benzylamines ,Neutrophils ,Clinical Biochemistry ,Regulator ,Review ,Research & Experimental Medicine ,Cyclams ,Biochemistry ,CXCR4 ,Chemokine receptor ,Mice ,Neutrophils. Guest Editor: Dirk Roos ,Bone Marrow ,Heterocyclic Compounds ,Medicine ,Homeostasis ,HMGB1 Protein ,General Clinical Medicine ,biology ,RAPID MOBILIZATION ,Imidazoles ,General Medicine ,3. Good health ,Cell biology ,HEMATOPOIETIC PROGENITOR CELLS ,medicine.anatomical_structure ,Medicine, Research & Experimental ,HUMAN-IMMUNODEFICIENCY-VIRUS ,CHEMOKINE RECEPTOR ,ANTAGONIST PLERIXAFOR ,medicine.symptom ,Warts ,WHIM-SYNDROME ,Life Sciences & Biomedicine ,retention ,Receptors, CXCR4 ,Cell Survival ,Primary Immunodeficiency Diseases ,BONE-MARROW ,Reviews ,Context (language use) ,Inflammation ,clearance ,G-CSF ,03 medical and health sciences ,Medicine, General & Internal ,General & Internal Medicine ,Hematologic Agents ,Animals ,Humans ,mobilization ,Serum Albumin ,Science & Technology ,business.industry ,Immunologic Deficiency Syndromes ,1103 Clinical Sciences ,IN-VITRO ,Chemokine CXCL12 ,Peptide Fragments ,030104 developmental biology ,STROMAL CELLS ,Mutation ,biology.protein ,Bone marrow ,business ,Spleen - Abstract
Background Chemokines play a critical role in orchestrating the distribution and trafficking of neutrophils in homeostasis and disease. Results The CXCR4/CXCL12 chemokine axis has been identified as a central regulator of these processes. Conclusion In this review, we focus on the role of CXCR4/CXCL12 chemokine axis in regulating neutrophil release from the bone marrow and the trafficking of senescent neutrophils back to the bone marrow for clearance under homeostasis and disease. We also discuss the role of CXCR4 in fine‐tuning neutrophil responses in the context of inflammation.
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- 2018
6. CXCR4 Ligands
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Ken Herrmann, Hans-Juergen Wester, Constantin Lapa, Annemiek M E Walenkamp, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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0301 basic medicine ,Receptors, CXCR4 ,Chemokine receptor CCR5 ,medicine.medical_treatment ,TUMOR-CELLS ,Medizin ,CHEMOKINE RECEPTOR CXCR4 ,ACUTE MYELOID-LEUKEMIA ,ANTI-PD-L1 ANTIBODY ,PHASE-2 TRIAL ,Pharmacology ,Ligands ,CXCR4 ,Targeted therapy ,03 medical and health sciences ,Chemokine receptor ,0302 clinical medicine ,Neoplasms ,MULTIPLE-MYELOMA ,Medicine ,Animals ,Humans ,tumor microenvironment ,endoradiotherapy ,Radiology, Nuclear Medicine and imaging ,Molecular Targeted Therapy ,Tumor microenvironment ,biology ,business.industry ,RAPID MOBILIZATION ,Cancer ,medicine.disease ,CXCR4-DIRECTED ENDORADIOTHERAPY ,Chemokine CXCL12 ,4 EXPRESSION ,030104 developmental biology ,MYOCARDIAL-INFARCTION ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,biology.protein ,immunotherapy ,Stem cell ,business - Abstract
The G protein-coupled protein receptor C-X-C chemokine receptor 4 (CXCR4) is an attractive target for cancer diagnosis and treatment, as it is overexpressed in many solid and hematologic cancers. Binding of its ligand, C-X-C chemokine ligand 12 (CXCL12), results in receptor internalization and activation of several signal transduction pathways, such as phosphoinositide 3-kinase/protein kinase B, which are critical in cell proliferation, angiogenesis, development of metastasis, and survival. Also, the CXCR4-CXCL12 axis is involved in the interaction between hematopoietic stem cells (as well as hematologic and solid tumor cells) and their protective microenvironment. This interaction can be disrupted by CXCR4 antagonists. This concept is being used clinically to harvest hematopoietic stem or progenitor cells from bone marrow and to sensitize cancer cells to conventional chemotherapy and radiotherapy, and the potential to overcome tumor microenvironment-driven immunosuppression is being explored. This review focuses on new strategies for improvement of cancer treatment by targeting of the CXCR4-CXCL12 interaction. Because of its critical role in cancer, many peptidic and nonpeptidic ligands with different modes of antagonistic activity against the CXCR4-CXCL12 axis have been developed, with some of them reaching clinical trials. Molecular imaging with recently developed radiolabeled CXCR4 ligands could facilitate the selection of patients who might benefit from directed targeted therapy, including CXCR4-directed endoradiotherapy.
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- 2017
7. The Ventral Resection of the Cervical Vertebral Body
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Armenise, B., Cancelliere, M., Montinaro, A., Grote, W., editor, Brock, M., editor, Clar, H.-E., editor, Klinger, M., editor, and Nau, H.-E, editor
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- 1980
- Full Text
- View/download PDF
8. Serpina1 is a potent inhibitor of IL-8-induced hematopoietic stem cell mobilization
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Gerjo A. Velders, Melissa van Pel, Ivan J. D. Lindley, Willem E. Fibbe, Roel Willemze, Henny Hagoort, Peter M. H. Heegaard, Ronald van Os, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Stem Cell Aging Leukemia and Lymphoma (SALL)
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Male ,ALPHA-1-PROTEINASE INHIBITOR ,Proteases ,INTERLEUKIN-8 ,Time Factors ,bone marrow ,BLOOD ,BONE-MARROW ,Blotting, Western ,protease inhibitors ,Biology ,Pharmacology ,Granulocyte ,Models, Biological ,RADIOPROTECTIVE CAPACITY ,Mice ,THIOPHILIC ADSORPTION ,medicine ,Cell Adhesion ,Animals ,adhesion molecules ,RNA, Messenger ,Progenitor cell ,Hematopoietic Stem Cell Mobilization ,Mice, Inbred BALB C ,Multidisciplinary ,Pancreatic Elastase ,Reverse Transcriptase Polymerase Chain Reaction ,Stem Cells ,RAPID MOBILIZATION ,Elastase ,Hematopoietic stem cell ,Antibodies, Monoclonal ,Dose-Response Relationship, Radiation ,protease ,Biological Sciences ,COLONY-STIMULATING FACTOR ,Colony-stimulating factor ,Hematopoietic Stem Cells ,Molecular biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,PROGENITOR CELLS ,alpha 1-Antitrypsin ,Cytokines ,Bone marrow ,RHESUS-MONKEYS - Abstract
Here, we report that cytokine-induced (granulocyte colony-stimulating factor and IL-8) hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) mobilization is completely inhibited after low-dose (0.5 Gy) total-body irradiation (TBI). Because neutrophil granular proteases are regulatory mediators in cytokine-induced HSC/HPC mobilization, we considered a possible role for protease inhibitors in the induction of HSC/HPC mobilization. Bone marrow (BM) extracellular extracts that were obtained from murine femurs after 0.5 Gy of TBI contained an inhibitor of elastase. Also, after low-dose TBI, both Serpina1 mRNA and protein concentrations were increased in BM extracts, compared with extracts that were obtained from controls. The inhibitory activity in BM extracts of irradiated mice was reversed by addition of an Ab directed against Serpina1. To further study a possiblein vivorole of Serpina1 in HSC/HPC mobilization, we administered Serpina1 before IL-8 injection. This administration resulted in an almost complete inhibition of HSC/HPC mobilization, whereas heat-inactivated Serpina1 had no effect. These results indicate that low-dose TBI inhibits cytokine-induced HSC/HPC mobilization and induces Serpina1 in the BM. Because exogenous administration of Serpina1 inhibits mobilization, we propose that radiation-induced Serpina1 is responsible for the inhibition of HSC/HPC mobilization. Also, we hypothesize that cytokine-induced HSC/HPC mobilization is determined by a critical balance between serine proteases and serine protease inhibitors.
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- 2006
9. Enhancement of G-CSF-induced stem cell mobilization by antibodies against the beta 2 integrins LFA-1 and Mac-1
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REPOPULATING ABILITY ,BONE-MARROW STROMA ,MONOCLONAL-ANTIBODY ,RAPID MOBILIZATION ,FLT-3 LIGAND ,COLONY-STIMULATING FACTOR ,PERIPHERAL-BLOOD ,IN-VIVO ,HEMATOPOIETIC PROGENITOR CELLS ,ADHESION MOLECULES - Abstract
The beta2 integrins leukocyte function antigen-1 (LFA-1, CD11a) and macrophage antigen-1 (Mac-1, CD11b) have been reported to play a role in the attachment of CD34(+) cells to stromal cells in the bone marrow. When administered prior to interleukin-8 (IL-8), anti-LFA-1 antibodies completely prevent the IL-8-induced mobilization of hematopoietic stem cells in mice. Here, we studied the role of anti-beta2 integrin antibodies in granulocyte colony-stimulating factor (G-CSF)-induced mobilization of hematopoietic progenitor cells. Administration of antibodies against the a chain of LFA-1 or against the a chain of Mac-1 followed by daily injections of G-CSF for more than 1 day resulted in a significant enhancement of mobilization of hematopoietic progenitor cells when compared with mobilization induced by G-CSF alone. Also, the number of late (day 28) cobblestone area-forming cells in vitro was significantly higher after mobilization with anti-LFA-1 antibodies followed by 5 mug G-CSF for 5 days than with G-CSF alone (119+/-34 days vs 17+/-14 days), indicating mobilization of repopulating stem cells. Pretreatment with blocking antibodies to intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of LFA-1 and Mac-1, did not result in an effect on G-CSF-induced mobilization, suggesting that the enhancing effect required an interaction of the beta2 integrins and one of their other ligands. Enhancement of mobilization was not observed in LFA-1-deficient (CD11a) mice, indicating that activated cells expressing LFA-1 mediate the synergistic effect, rather than LFA-1-mediated adhesion.
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- 2002
10. Enhancement of G-CSF–induced stem cell mobilization by antibodies against the β2 integrins LFA-1 and Mac-1
- Author
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Evert-Jan F. M. de Kruijf, J.F.M. Pruijt, Gerjo A. Velders, Willem E. Fibbe, Roel Willemze, Perry Verzaal, Ronald van Os, Yvette van Kooyk, Carl G. Figdor, Molecular cell biology and Immunology, CCA - Cancer biology and immunology, AII - Cancer immunology, AII - Inflammatory diseases, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Stem Cell Aging Leukemia and Lymphoma (SALL)
- Subjects
Male ,medicine.medical_specialty ,Stromal cell ,MONOCLONAL-ANTIBODY ,Immunology ,CD34 ,Macrophage-1 Antigen ,Bone Marrow Cells ,PERIPHERAL-BLOOD ,Biochemistry ,ADHESION MOLECULES ,Colony-Forming Units Assay ,Mice ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,medicine ,Animals ,IN-VIVO ,Mice, Knockout ,REPOPULATING ABILITY ,Mice, Inbred BALB C ,BONE-MARROW STROMA ,Blood Cells ,biology ,Cell adhesion molecule ,RAPID MOBILIZATION ,FLT-3 LIGAND ,Antibodies, Monoclonal ,Drug Synergism ,Cell Biology ,Hematology ,COLONY-STIMULATING FACTOR ,Hematopoietic Stem Cells ,Colony-stimulating factor ,Molecular biology ,Hematopoietic Stem Cell Mobilization ,Lymphocyte Function-Associated Antigen-1 ,HEMATOPOIETIC PROGENITOR CELLS ,Haematopoiesis ,medicine.anatomical_structure ,Endocrinology ,Integrin alpha M ,CD18 Antigens ,biology.protein ,Bone marrow ,Stem cell ,Tumorimmunology ,Haematology - Abstract
Item does not contain fulltext The beta 2 integrins leukocyte function antigen-1 (LFA-1, CD11a) and macrophage antigen-1 (Mac-1, CD11b) have been reported to play a role in the attachment of CD34(+) cells to stromal cells in the bone marrow. When administered prior to interleukin-8 (IL-8), anti-LFA-1 antibodies completely prevent the IL-8-induced mobilization of hematopoietic stem cells in mice. Here, we studied the role of anti-beta 2 integrin antibodies in granulocyte colony-stimulating factor (G-CSF)-induced mobilization of hematopoietic progenitor cells. Administration of antibodies against the alpha chain of LFA-1 or against the alpha chain of Mac-1 followed by daily injections of G-CSF for more than 1 day resulted in a significant enhancement of mobilization of hematopoietic progenitor cells when compared with mobilization induced by G-CSF alone. Also, the number of late (day 28) cobblestone area-forming cells in vitro was significantly higher after mobilization with anti-LFA-1 antibodies followed by 5 microg G-CSF for 5 days than with G-CSF alone (119 +/- 34 days vs 17 +/- 14 days), indicating mobilization of repopulating stem cells. Pretreatment with blocking antibodies to intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of LFA-1 and Mac-1, did not result in an effect on G-CSF-induced mobilization, suggesting that the enhancing effect required an interaction of the beta 2 integrins and one of their other ligands. Enhancement of mobilization was not observed in LFA-1-deficient (CD11a) mice, indicating that activated cells expressing LFA-1 mediate the synergistic effect, rather than LFA-1-mediated adhesion.
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- 2002
11. Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice
- Author
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Ronald van Os, Marianke L J Van Schie, Sofie Starckx, Ivan J. D. Lindley, Annunciata Vecchi, Alberto Mantovani, Evert Jan F M De Kruijf, Ghislain Opdenakker, Willem E. Fibbe, Perry Verzaal, Roel Willemze, J.F.M. Pruijt, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Stem Cell Aging Leukemia and Lymphoma (SALL)
- Subjects
EXPRESSION ,Neutropenia ,Time Factors ,bone marrow ,Neutrophils ,Population ,Biology ,G-CSF ,PERIPHERAL-BLOOD ,GELATINASE-B ,BONE-MARROW CELLS ,metalloproteinases ,RADIOPROTECTIVE CAPACITY ,Mice ,medicine ,Animals ,adhesion molecules ,Interleukin 8 ,Progenitor cell ,education ,Hematopoietic Stem Cell Mobilization ,Cells, Cultured ,education.field_of_study ,Mice, Inbred BALB C ,Multidisciplinary ,Dose-Response Relationship, Drug ,RAPID MOBILIZATION ,Interleukin-8 ,Antibodies, Monoclonal ,ADHESION MOLECULE-1 ,hemic and immune systems ,Biological Sciences ,COLONY-STIMULATING FACTOR ,medicine.disease ,Colony-stimulating factor ,Flow Cytometry ,Hematopoietic Stem Cells ,Neutrophilia ,Recombinant Proteins ,medicine.anatomical_structure ,Matrix Metalloproteinase 9 ,PROGENITOR CELLS ,Immunology ,Bone marrow ,medicine.symptom ,MMP-9 ,RHESUS-MONKEYS - Abstract
The CXC chemokine interleukin-8 (IL-8/CXCL8) induces rapid mobilization of hematopoietic progenitor cells (HPCs). Previously we showed that mobilization could be prevented completely in mice by pretreatment with neutralizing antibodies against the β2-integrin LFA-1 (CD11a). In addition, murine HPCs do not express LFA-1, indicating that mobilization requires a population of accessory cells. Here we show that polymorphonuclear cells (PMNs) serve as key regulators in IL-8-induced HPC mobilization. The role of PMNs was studied in mice rendered neutropenic by administration of a single injection of antineutrophil antibodies. Absolute neutropenia was observed up to 3–5 days with a rebound neutrophilia at day 7. The IL-8-induced mobilizing capacity was reduced significantly during the neutropenic phase, reappeared with recurrence of the PMNs, and was increased proportionally during the neutrophilic phase. In neutropenic mice, the IL-8-induced mobilizing capacity was restored by the infusion of purified PMNs but not by infusion of mononuclear cells. Circulating metalloproteinase gelatinase B (MMP-9) levels were detectable only in neutropenic animals treated with PMNs in combination with IL-8, showing thatin vivoactivated PMNs are required for the restoration of mobilization. However, IL-8-induced mobilization was not affected in MMP-9-deficient mice, indicating that MMP-9 is not indispensable for mobilization. These data demonstrate that IL-8-induced mobilization of HPCs requires thein vivoactivation of circulating PMNs.
- Published
- 2002
12. In Brief: Assessing DOD's New Strategic Guidance
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LIBRARY OF CONGRESS WASHINGTON DC CONGRESSIONAL RESEARCH SERVICE, Dale, Catherine, Towell, Pat, LIBRARY OF CONGRESS WASHINGTON DC CONGRESSIONAL RESEARCH SERVICE, Dale, Catherine, and Towell, Pat
- Abstract
On January 5, 2012, President Obama announced new defense strategic guidance entitled Sustaining U.S. Global Leadership: Priorities for 21st Century Defense. This new guidance is significant because it is explicitly intended to reshape future Department of Defense (DoD) priorities, activities, and budget requests for the next decade. While the guidance is intended to steer DoD decision-making as it reduces defense spending by about $487 billion over the next 10 years to meet the initial budget caps set in the Budget Control Act (BCA) of 2011, it does not account for the possibility of sequestration -- further significant, across-the-board cuts that could be required pursuant to implementation of the BCA. Defense officials have stated that, were they directed to find an additional $500 billion in cuts, this guidance would not apply, and DoD would have to shed missions and commitments and capabilities that we believe are necessary to protect core U.S. national security interests. This CRS report highlights and analyzes key strategic-level issues raised by the new guidance. The report will not be updated., CRS Report for Congress.
- Published
- 2012
13. Rapid Deployment: A Vital Trump
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ARMY WAR COLL CARLISLE BARRACKS PA, Kelley, P. X., ARMY WAR COLL CARLISLE BARRACKS PA, and Kelley, P. X.
- Abstract
The View From the Fourth Estate feature of the September 1980 issue of Parameters reprinted an article by Thomas Toch ("Rapid Deployment: A Questionable Trump") which was critical of both the strategic concept of a US Rapid Deployment Force and the practical steps being taken to bring it to fruition. In the interest of providing readers a balanced perspective, Parameters invited Marine Corps Lieutenant General P. X. Kelley, Commander of the Rapid Deployment Joint Task Force, to provide an authoritative public reply. The article below was submitted in response to Parameters' invitation., Published in Parameters, v11 n1 p50-53, 1981.
- Published
- 1981
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