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

• Published in: Blood 2002-07, Vol.100 (1), p.327
• Main Authors: Velders, Gerjo A, Pruijt, Johannes F M, Verzaal, Perry, van Os, Ronald, van Kooyk, Yvette, Figdor, Carl G, de Kruijf, Evert-Jan F M, Willemze, Roel, Fibbe, Willem E
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - pharmacology; Blood Cells - cytology; Blood Cells - drug effects; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; CD18 Antigens - immunology; Colony-Forming Units Assay; Drug Synergism; Granulocyte Colony-Stimulating Factor - pharmacology; Hematopoietic Stem Cell Mobilization - methods; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Lymphocyte Function-Associated Antigen-1 - immunology; Macrophage-1 Antigen - immunology; Male; Mice; Mice, Inbred BALB C; Mice, Knockout
• ISSN: 0006-4971
• DOI: 10.1182/blood.V100.1.327

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.