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Blood, Vol. 95 No. 2 (January 15), 2000:
pp. 453-460
CD13/N-aminopeptidase is involved in the development of dendritic
cells and macrophages from cord blood CD34+ cells
Michelle Rosenzwajg,
Ludovic Tailleux, and
Jean
Claude Gluckman
From the Laboratoire de Biologie et Thérapeutique des
Pathologies Immunitaires, Université Paris 6-Centre National de
la Recherche Scientifique (ESA 7087), and the Laboratoire
d'Immunologie Cellulaire de l'Ecole Pratique des Hautes Etudes,
Hôpital Pitié-Salpêtrière, Paris, France.
Expression of CD13/N-aminopeptidase may reflect cell activation and
growth. We examined its role regarding cell growth in cultures of cord
blood CD34+ cells with stem cell factor/Flt-3
ligand/granulocyte-macrophage colony-stimulating factor/tumor
necrosis factor- . Indeed, 82% ± 6% of cells from culture
day 5 were CD13hi, 25% ± 8% of which were still
Lin . About 50% of CD13hiLin cells, which comprise
progenitors of dendritic cells (DC), monocytes/macrophages and
granulocytes, and 30% of CD13loLin cells were
CD34+. Sorted CD34+CD13hiLin
cells, cultured further for 7 days with the same
cytokines, expanded 31-fold and
CD34-CD13hiLin cells 7-fold, but
CD34+CD13loLin and
CD34 CD13loLin cells did not grow. Thus,
cell growth correlated with CD13 expression, all the more so that cells
were CD34+. Actinonin, the most potent N-aminopeptidase
inhibitor, was used to engage CD13 on sorted CD13hiLin
cells and on culture day-7 bulk cells. In both cases, this resulted in
reversible cell growth arrest, with 30% to 60% fewer cells in the
G2/S-M phase than in controls. Interestingly, similar effects were
noted with CD13 monoclonal antibody TÜK1, which does not
inhibit N-aminopeptidase activity, but not with
N-aminopeptidase-blocking antibodies WM15 and F23. All cycling cells
appeared susceptible to actinonin, which induced cell apoptosis at the
same time as Bcl-2 was downregulated and caspase-3 activity increased,
but finally percentages and yields of DC and macrophage precursors were
affected more than those of granulocytic cells. Thus, through engagement of N-aminopeptidase enzymatic site but possibly also of an
independent determinant, CD13 plays a role in the growth of
DC/macrophage progenitors and precursors.
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