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Induction of LFA-1 on pluripotent CD34+ bone marrow cells does not affect
lineage commitment
R Torensma, RA Raymakers, Y van Kooyk and CG Figdor
Tumor Immunology Laboratory, University Hospital St. Radboud, Nijmegen, The
Netherlands.
Leukocyte function associated antigen 1 (LFA-1) is an adhesion molecule
indispensable in immune and inflammatory reactions, but its role in
hematopoiesis remains obscure. Since LFA-1 is predominantly expressed by
leukocytes, it is considered as a marker of late stage stem cell maturation
when expressed on CD34+ bone marrow cells, and represents more mature
hematopoietic progenitor cells. We observed that freshly isolated CD34+
bone marrow cells express LFA-1, and that the level of expression is highly
variable. Interestingly, the expression of LFA-1 specific activation
epitope L16 on these cells is low, even after culture. This demonstrates
the LFA-1 is not activated, as was confirmed by low adhesion to ICAM-1.
Culturing sorted CD34+ LFA-1+ cells in single cell per well assays in
medium supplemented with SCF, Epo, IL-3, Il-6, GM-CSF, and G-CSF revealed
that they gave rise to dispersed macrophage-like colonies, supporting the
notion that CD34+LFA-1+ cells indeed consist of a mature committed cell
population. In contrast, sorted CD34+LFA-1- cells had high proliferative
potential and developed into large multilineage colonies within 14 days of
culture. Unanticipated, in time course experiments we observed that these
CD34+LFA-1- cells expressed LFA-1 within 24 hours upon culture. This
induction was neither caused by the monoclonal antibody used to tag CD34
cells, nor dependent on growth factors present in the medium. These
findings demonstrate that two populations of CD34+LFA-1+ cells can be
discriminated: leukocyte lineage committed CD34+ cells in freshly isolated
bone marrow cells, and multipotent CD34+ cells that acquired LFA-1 upon in
vitro culture. These in vitro findings support the hypothesis that once
contacts with bone marrow stroma are lost, LFA- 1 is upregulated by
default, due to the lack of negative regulating signals from stromal cells.
This might also explain the widely variable expression of LFA-1 as a result
of crowding of cells in the bone marrow with subsequent loss of contact
with stroma and upregulation of LFA-1, providing those cells with adhesion
receptors enabling migration in the periphery.
Volume 87,
Issue 10,
pp. 4120-4128,
05/15/1996
Copyright © 1996 by The American Society of Hematology
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