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 journalArticlepeer-review

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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