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Anti-LFA-1 Blocking Antibodies Prevent Mobilization of
Hematopoietic Progenitor Cells Induced by Interleukin-8
Johannes F.M. Pruijt,
Yvette van Kooyk,
Carl G. Figdor,
Ivan J.D. Lindley,
Roel Willemze, and
Willem E. Fibbe
From the Laboratory of Experimental Hematology, the Department of
Hematology, Leiden University Medical Center, Leiden; the Department of
Tumor Immunology, University Hospital Nijmegen, The Netherlands; and
Novartis Forschungsinstitut, Vienna, Austria.
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
 2-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 2-integrin LFA-1
in the IL-8-induced mobilization of hematopoietic stem cells.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4099-4105
© 1998 by The American Society of Hematology.
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