Anti–LFA-1 Blocking Antibodies Prevent Mobilization of Hematopoietic Progenitor Cells Induced by Interleukin-8

• Published in: Blood Vol. 91; no. 11; pp. 4099 - 4105
• Main Authors: Pruijt, Johannes F.M., van Kooyk, Yvette, Figdor, Carl G., Lindley, Ivan J.D., Willemze, Roel, Fibbe, Willem E.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.06.1998; The Americain Society of Hematology
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antibodies - pharmacology; Biological and medical sciences; Blood Cell Count; Bone marrow, stem cells transplantation. Graft versus host reaction; Colony-Forming Units Assay; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - physiology; Integrin alpha4beta1; Integrins - immunology; Integrins - physiology; Intercellular Adhesion Molecule-1 - immunology; Intercellular Adhesion Molecule-1 - physiology; Interleukin-8 - pharmacology; Lymphocyte Function-Associated Antigen-1 - immunology; Lymphocyte Function-Associated Antigen-1 - physiology; Medical sciences; Mice; Mice, Inbred BALB C; Monocytes - transplantation; Receptors, Lymphocyte Homing - immunology; Receptors, Lymphocyte Homing - physiology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Whole-Body Irradiation; Stem cell; Cytokine; Rodentia; Cell adhesion molecule; Hematopoietic cell; Blood; Chemokine; Mobilization; Vertebrata; Autograft; Mammalia; Integrin; Mouse; Animal; Graft; Interleukin 8
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V91.11.4099

Previously, we have shown that interleukin (IL)-8 induces the rapid (15 to 30 minutes) mobilization of hematopoietic progenitor cells (HPC) in mice. Because integrins are essential for adhesion and transendothelial migration of HPC, we studied the involvement of the β2-integrin leukocyte function-associated antigen-1 (LFA-1) in IL-8–induced mobilization. After a single injection of blocking anti–LFA-1 antibodies, no mobilization of colony-forming cells was observed. In addition, when mice were pretreated with anti–LFA-1 or saline and subsequently injected with 30 μg of IL-8, mobilization of HPC was completely blocked. We showed that this was not due to anti–LFA-1 antibodies affecting colony formation, as addition of anti–LFA-1 antibodies to colony cultures in semisolid medium had no inhibitory activity. Also, anti-intercellular adhesion molecule (ICAM)-1 antibodies, directed to the main ligand of LFA-1 significantly inhibited the IL-8–induced mobilization. Furthermore, IL-1–induced mobilization was significantly inhibited by anti–LFA-1 antibodies. Because LFA-1 is reported to be expressed on more differentiated HPC, it was considered that the IL-8–induced mobilization of more primitive HPC would not be blocked by anti–LFA-1 antibodies. Transplantation of blood-derived mononuclear cells (MNC) from IL-8–mobilized animals pretreated with anti–LFA-1 antibodies protected only 25% of lethally irradiated recipient mice, whereas the radioprotection rate of control mice transplanted with MNC derived from IL-8-mobilized animals was 86% (P < .01). Anti-LFA–1 antibodies did not interfere with stem cell homing, as transplantation of IL-8-mobilized blood MNC, incubated in vitro with these antibodies resulted in 100% radioprotection. We conclude that anti–LFA-1 antibodies completely prevent the rapid mobilization of colony-forming cells and of cells with radioprotective capacity induced by IL-8. These results indicate a major role for the β2-integrin LFA-1 in the IL-8–induced mobilization of hematopoietic stem cells.