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Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 107-112
Murine Hematopoietic Progenitor Cells With Colony-Forming or
Radioprotective Capacity Lack Expression of the
 2-Integrin LFA-1
Johannes F.M. Pruijt,
Yvette van Kooyk,
Carl G. Figdor,
Roel Willemze, and
Willem E. Fibbe
From the Laboratory of Experimental Hematology, Department of
Hematology, Leiden University Medical Center, Leiden; and the
Department of Tumor Immunology, University Hospital Nijmegen, Nijmegen,
The Netherlands.
Recently, we have demonstrated that antibodies that block the
function of the  2-integrin leukocyte function-associated
antigen-1 (LFA-1) completely abrogate the rapid mobilization of
hematopoietic progenitor cells (HPC) with colony-forming and
radioprotective capacity induced by interleukin-8 (IL-8) in mice. These
findings suggested a direct inhibitory effect of these antibodies on
LFA-1-mediated transmigration of stem cells through the bone marrow
endothelium. Therefore, we studied the expression and functional role
of LFA-1 on murine HPC in vitro and in vivo. In steady state bone
marrow ± 50% of the mononuclear cells (MNC) were
LFA-1neg. Cultures of sorted cells, supplemented with
granulocyte colony-stimulating factor (G-CSF)/granulocyte-macrophage
colony-stimulating factor (GM-CSF)/IL-1/IL-3/IL-6/stem cell factor
(SCF) and erythropoietin (EPO) indicated that the
LFA-1neg fraction contained the majority of the
colony-forming cells (CFCs) (LFA-1neg 183 ± 62/7,500 cells v LFA-1pos 29 ± 17/7,500 cells,
P < .001). We found that the radioprotective capacity resided
almost exclusively in the LFA-1neg cell fraction, the
radioprotection rate after transplantation of 103, 3 × 103, 104, and 3 × 104 cells being
63%, 90%, 100%, and 100% respectively. Hardly any radioprotection
was obtained from LFA-1pos cells. Similarly, in cytokine
(IL-8 and G-CSF)-mobilized blood, the LFA-1neg fraction,
which comprised 5% to 10% of the MNC, contained the majority of the
colony-forming cells, as well as almost all cells with radioprotective
capacity. Subsequently, primitive bone marrow-derived HPC, represented
by Wheat-germ-agglutinin (WGA)+/Lineage
(Lin) /Rhodamine (Rho) sorted cells, were
examined. More than 95% of the Rho cells were
LFA-1neg. Cultures of sorted cells showed that the
LFA-1neg fraction contained all CFU. Transplantation of 150 Rho LFA-1neg or up to 600 RhoLFA-1pos cells protected 100% and 0% of
lethally irradiated recipient mice, respectively. These results show
that primitive murine HPC in steady-state bone marrow and of
cytokine-mobilized blood do not express LFA-1.
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