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Proteolytic enzyme levels are increased during granulocyte colony-stimulating factor-induced hematopoietic stem cell mobilization in human donors but do not predict the number of mobilized stem cells

Van Os, R., Van Schie, MLJ., Willemze, R. & Fibbe, WE., Jul-2004, In : Journal of hematotherapy & stem cell research. 11, 3, p. 513-521 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • R Van Os
  • MLJ Van Schie
  • R Willemze
  • WE Fibbe

Previous studies from our laboratory indicate that functional, mature neutrophils are essential for interleukin-8 (IL-8)-induced stem cell mobilization. To study a possible role of neutrophils in granulocyte colony-stimulating factor (G-CSF) induced hematopoietic mobilization, we assessed the number of circulating CD34(+) cells in healthy allogeneic stem cell donors on days 3, 4, and 5 of mobilization for comparison with the number of peripheral blood neutrophils and the plasma levels of IL-8, Flt3 ligand (FL), matrix metalloproteinase-9 (MMP-9), and human neutrophil elastase (HNE). Thirty-seven of 45 donors required 1 day of apheresis to obtain 5 x 10(6) CD34(+)/kg recipient body weight (high responders), the remaining 8 donors required I extra day of apheresis on day 6 (low responders). On day 5, CD34(+) numbers in the blood were significantly higher in high responders (116 x 10(3) +/- 10.4/ml) than in low responders (54.1 x 10(3) +/- 10.3, p <0.001). In all donors, MMP-9 and HNE levels were increased compared to nonmobilized individuals, but in high responders, plasma MMP-9 levels on days 3-5 of mobilization were substantially higher than in low responders (p &LE; 0.02 for MMP-9 and p = 0.89, p = 0.05 and p = 0.52 for HNE on days 3, 4, and 5, respectively). These results are in accordance with the hypothesis that neutrophils play a role in G-CSF-induced mobilization through the release of proteases such as MMP-9 and elastase. No change in plasma levels of IL-8 or Flt3 ligand was observed, suggesting that these cytokines do not play a role in stem cell mobilization. However, because stem cell numbers could not be predicted by proteolytic enzyme levels and/or neutrophil numbers, other undefined factors may be more important.

Original languageEnglish
Pages (from-to)513-521
Number of pages9
JournalJournal of hematotherapy & stem cell research
Volume11
Issue number3
Publication statusPublished - Jul-2004
Externally publishedYes

    Keywords

  • PERIPHERAL-BLOOD, PROGENITOR CELLS, CD34(+) CELLS, ADHESION MOLECULES, HUMAN NEUTROPHILS, PLASMA-LEVELS, INTERLEUKIN-8, ANTIBODIES, MARROW, METALLOPROTEINASES

ID: 13961058