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

Gerjo A Velders, Johannes F M Pruijt, Perry Verzaal, Ronald van Os, Yvette van Kooyk, Carl G Figdor, Evert-Jan F M de Kruijf, Roel Willemze, Willem E Fibbe

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The beta 2 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-beta 2 integrin antibodies in granulocyte colony-stimulating factor (G-CSF)-induced mobilization of hematopoietic progenitor cells. Administration of antibodies against the alpha chain of LFA-1 or against the alpha 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 microg 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 beta 2 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)327-33
Number of pages7
Issue number1
Publication statusPublished - 1 Jul 2002


  • Animals
  • Antibodies, Monoclonal/administration & dosage
  • Blood Cells/cytology
  • Bone Marrow Cells/cytology
  • CD18 Antigens/immunology
  • Colony-Forming Units Assay
  • Drug Synergism
  • Granulocyte Colony-Stimulating Factor/pharmacology
  • Hematopoietic Stem Cell Mobilization/methods
  • Hematopoietic Stem Cells/cytology
  • Lymphocyte Function-Associated Antigen-1/immunology
  • Macrophage-1 Antigen/immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout

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