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Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice

Pruijt, JFM., Verzaal, P., van Os, R., de Kruijf, EJFM., van Schie, MLJ., Mantovani, A., Vecchi, A., Lindley, IJD., Willemze, R., Starckx, S., Opdenakker, G. & Fibbe, WE., 30-Apr-2002, In : Proceedings of the National Academy of Science of the United States of America. 99, 9, p. 6228-6233 6 p.

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  • Pruiijt PNAS neutrophils 2002

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DOI

  • JFM Pruijt
  • P Verzaal
  • R van Os
  • EJFM de Kruijf
  • MLJ van Schie
  • A Mantovani
  • A Vecchi
  • IJD Lindley
  • R Willemze
  • S Starckx
  • G Opdenakker
  • WE Fibbe

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 beta2-integrin LFA-1 (CID11a). 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 that in vivo activated 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 the in vivo activation of circulating PMNs.

Original languageEnglish
Pages (from-to)6228-6233
Number of pages6
JournalProceedings of the National Academy of Science of the United States of America
Volume99
Issue number9
Publication statusPublished - 30-Apr-2002

    Keywords

  • metalloproteinases, MMP-9, adhesion molecules, bone marrow, G-CSF, COLONY-STIMULATING FACTOR, BONE-MARROW CELLS, PROGENITOR CELLS, GELATINASE-B, ADHESION MOLECULE-1, RADIOPROTECTIVE CAPACITY, RAPID MOBILIZATION, PERIPHERAL-BLOOD, RHESUS-MONKEYS, EXPRESSION

ID: 13961002