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

Johannes F M Pruijt, Perry Verzaal, Ronald Van Os, Evert Jan F M De Kruijf, Marianke L J Van Schie, Alberto Mantovani, Annunciata Vecchi, Ivan J D Lindley, Roel Willemze, Sofie Starckx, Ghislain Opdenakker, Willem E. Fibbe

Research output: Contribution to journalArticle

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 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 Sciences of the United States of America
Volume99
Issue number9
DOIs
Publication statusPublished - Apr 30 2002

Keywords

  • Adhesion molecules
  • Bone marrow
  • G-CSF
  • Metalloproteinases
  • MMP-9

ASJC Scopus subject areas

  • Genetics
  • General

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  • Cite this

    Pruijt, J. F. M., Verzaal, P., Van Os, R., De Kruijf, E. J. F. M., Van Schie, M. L. J., Mantovani, A., Vecchi, A., Lindley, I. J. D., Willemze, R., Starckx, S., Opdenakker, G., & Fibbe, W. E. (2002). Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice. Proceedings of the National Academy of Sciences of the United States of America, 99(9), 6228-6233. https://doi.org/10.1073/pnas.092112999