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Dendritic cells and macrophages can mature independently from a human bone
marrow-derived, post-colony-forming unit intermediate
P Szabolcs, D Avigan, S Gezelter, DH Ciocon, MA Moore, RM Steinman and JW Young
Laboratory of Cellular Physiology and Immunology, The Rockefeller
University, New York 10021-6399, USA.
CD34+ precursors in normal human bone marrow (BM) generate large numbers of
dendritic cells alongside macrophages and granulocytic precursors when
cultured for 12 to 14 days in c-kit ligand, granulocyte- macrophage
colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha
(TNF-alpha). This study reports an intermediate cell type that develops by
day 6, and has the potential to differentiate into either macrophages or
dendritic cells. When the d6 progeny are depleted of mature macrophages and
residual CD34+ precursors, a discrete CD14+ HLA-DR+ population persists in
addition to immunostimulatory CD14- HLA- DR() dendritic cells. Half of the
CD14+ HLA-DR+ population is in cell cycle (Ki-67+), but colony-forming
units (CFUs) are no longer detectable. The calls are c-fms+, but lack
myeloperoxidase and nonspecific esterase. They also possess substantial
phagocytic and allostimulatory activity. These post-CFU, CD14+ HLA-DR+
intermediates develop into typical macrophages when recultured in the
absence of exogenous cytokines. M-CSF supports up to approximately 2.5-fold
expansion of macrophage progeny. In contrast, the combination of GM-CSF and
TNF-alpha supports quantitative differentiation into dendritic cells,
lacking c-fms, CD14, and other macrophage properties, and expressing
HLA-DR, CD1a, CD83, CD80, CD86, and potent allostimulatory activity.
Therefore, normal CD34+ BM precursors can generate a post-CFU bipotential
intermediate in the presence of c-kit ligand, GM-CSF, and TNF-alpha. This
intermediate cell type will develop along the dendritic cell pathway when
macrophages are removed and GM-CSF and TNF-alpha are provided.
Alternatively, it can differentiate along a macrophage pathway when
recultured with or without M-CSF.
Volume 87,
Issue 11,
pp. 4520-4530,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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