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Granulocytic and monocytic differentiation of CD34hi cells is associated
with distinct changes in the expression of the PU.1- regulated molecules,
CD64 and macrophage colony-stimulating factor receptor
J Olweus, PA Thompson and F Lund-Johansen
Becton Dickinson Immunocytometry Systems, San Jose, CA 95131-1807, USA.
The present study investigated the possibility that macrophage colony-
stimulating factor (M-CSF) responsiveness of hematopoietic progenitor cells
is regulated at the level of receptor expression and that M-CSF receptor
(M-CSFR) may be used as an early marker of monocyte lineage commitment.
Immunofluorescence measurements with an anti-M-CSFR antibody showed that
44% +/- 5% of CD34hi cells expressed the receptor. The M-CSFR was present
on progenitor cells that were positive for the granulo-monocytic marker
CD64, but not on primitive, erythroid, or lymphoid progenitors. The
CD34hiCD64+ population could be divided into subsets of M-CSFRhi and
M-CSFRlo cells. In addition, a subset of CD34hiCD64-M-CSFRhi cells was
found. CD34+ cells that were positive for M-CSFR, CD64, or both gave rise
exclusively to granulo-monocytic cells, and 65% of the granulomonocytic
colony-forming cells in the CD34+ population were recovered from these
cells. Approximately 70% of the colony-forming cells (CFCs) derived from
CD34hiM-CSFRhi cells were macrophage colony-forming units (CFU-M), whereas
91% of the CFCs in the CD34hiCD64+M-CSFRlo population were granulocyte
colony-forming units (CFU-G). The M-CSFRhi cells with the highest frequency
of colony- forming and bipotent cells and largest average colony size were
found in the CD64- subset, indicating that M-CSFR appears earlier than CD64
during monocyte development. After 60 hours in culture, a subset of the
CD34hiM-CSFRhi cells had downmodulated M-CSFR (29% to 38%). This population
gave rise almost exclusively to granulocytes, whereas the cells that
remained M-CSFRhi gave rise exclusively to monocytes. In all experiments,
the M-CSFRhi population responded to M-CSF, whereas minimal responses were
observed among M-CSFRlo cells. These results suggest that M-CSF target
specificity among human hematopoietic progenitor cells is determined by
lineage-specific regulation of the M- CSFR and show that M-CSFR is a useful
marker to discriminate between monocytic and granulocytic progenitor cells.
Volume 88,
Issue 10,
pp. 3741-3754,
11/15/1996
Copyright © 1996 by The American Society of Hematology
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