Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice
Autor: | 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 |
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Přispěvatelé: | Damage and Repair in Cancer Development and Cancer Treatment (DARE), Stem Cell Aging Leukemia and Lymphoma (SALL) |
Jazyk: | angličtina |
Rok vydání: | 2002 |
Předmět: |
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 |
Zdroj: | Proceedings of the National Academy of Science of the United States of America, 99(9), 6228-6233. NATL ACAD SCIENCES |
ISSN: | 0027-8424 |
DOI: | 10.1073/pnas.092112999 |
Popis: | 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. |
Databáze: | OpenAIRE |
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