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Enhancement of G-CSF-induced stem cell mobilization by antibodies against the beta 2 integrins LFA-1 and Mac-1

Velders, GA., Pruijt, JFM., Verzaal, P., van Os, R., van Kooyk, Y., Figdor, CG., de Kruijf, EJFM., Willemze, R. & Fibbe, WE., 1-Jul-2002, In : Blood. 100, 1, p. 327-333 7 p.

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Documents

  • GA Velders
  • JFM Pruijt
  • P Verzaal
  • R van Os
  • Y van Kooyk
  • CG Figdor
  • EJFM de Kruijf
  • R Willemze
  • WE Fibbe

The beta2 integrins leukocyte function antigen-1 (LFA-1, CD11a) and macrophage antigen-1 (Mac-1, CD11b) have been reported to play a role in the attachment of CD34(+) cells to stromal cells in the bone marrow. When administered prior to interleukin-8 (IL-8), anti-LFA-1 antibodies completely prevent the IL-8-induced mobilization of hematopoietic stem cells in mice. Here, we studied the role of anti-beta2 integrin antibodies in granulocyte colony-stimulating factor (G-CSF)-induced mobilization of hematopoietic progenitor cells. Administration of antibodies against the a chain of LFA-1 or against the a chain of Mac-1 followed by daily injections of G-CSF for more than 1 day resulted in a significant enhancement of mobilization of hematopoietic progenitor cells when compared with mobilization induced by G-CSF alone. Also, the number of late (day 28) cobblestone area-forming cells in vitro was significantly higher after mobilization with anti-LFA-1 antibodies followed by 5 mug G-CSF for 5 days than with G-CSF alone (119+/-34 days vs 17+/-14 days), indicating mobilization of repopulating stem cells. Pretreatment with blocking antibodies to intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of LFA-1 and Mac-1, did not result in an effect on G-CSF-induced mobilization, suggesting that the enhancing effect required an interaction of the beta2 integrins and one of their other ligands. Enhancement of mobilization was not observed in LFA-1-deficient (CD11a) mice, indicating that activated cells expressing LFA-1 mediate the synergistic effect, rather than LFA-1-mediated adhesion.

Original languageEnglish
Pages (from-to)327-333
Number of pages7
JournalBlood
Volume100
Issue number1
Publication statusPublished - 1-Jul-2002

    Keywords

  • COLONY-STIMULATING FACTOR, HEMATOPOIETIC PROGENITOR CELLS, BONE-MARROW STROMA, PERIPHERAL-BLOOD, REPOPULATING ABILITY, MONOCLONAL-ANTIBODY, ADHESION MOLECULES, RAPID MOBILIZATION, FLT-3 LIGAND, IN-VIVO

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