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Recombinant human macrophage colony-stimulating factor in nonhuman
primates: selective expansion of a CD16+ monocyte subset with phenotypic
similarity to primate natural killer cells
DH Munn, AG Bree, AC Beall, MD Kaviani, H Sabio, RG Schaub, RK Alpaugh, LM Weiner and SJ Goldman
Division of Pediatric Hematology-Oncology, Medical College of Georgia,
Augusta, USA.
The CD16 receptor (Fc gamma R-III) is found on many tissue macrophages (M
phi s), but its expression on circulating monocytes is restricted to a
small, phenotypically distinct subset. The number of these CD16+ monocytes
may be markedly increased in response to sepsis, human immunodeficiency
virus infection, or metastatic malignancy. We have recently shown that the
CD16+ monocyte population is selectively expanded by administration of
recombinant human macrophage colony- stimulating factor (rhM-CSF). In the
current study, we used the highly rhM-CSF-responsive cynomolgus primate
model to further characterize this novel monocyte population. Animals
treated with rhM-CSF underwent a progressive and essentially complete
conversion to the CD16+ monocyte phenotype, with up to a 50-fold increase
in the number of CD16+ cells. This increase was paralleled by the emergence
of a population of circulating cells that morphologically resembled large
granular lymphocytes (LGLs). However, quantitatively, this population
corresponded closely to the number of CD16+ monocytes, and fluorescence-
activated cell sorting (FACS) confirmed that they were the same. In
addition to their LGL-like morphology, many rhM-CSF-induced CD16+ monocytes
showed a pattern of size, granularity, and quantitative cell surface marker
expression that closely resembled the pretreatment LGL/natural killer (NK)
cell population but that did not resemble the pretreatment monocyte
population. However, rhM-CSF-induced CD16+ monocytes could be distinguished
from LGL/ NK cells by fact that they all expressed cell surface receptors
for rhM-CSF, and many of them showed reduced but detectable phagocytic and
respiratory burst activity. Studies of human subjects treated with rhM-CSF
also showed an analogous population of "LGL-appearing" CD16+ mononuclear
cells. Thus, our studies reveal a previously unsuspected ability of cells
in the monocyte lineage to adopt a phenotype similar to that of LGL/NK
cells. The extent of this phenotypic convergence suggests that the two
lineages retain access to elements of a similar developmental pathway.
Volume 88,
Issue 4,
pp. 1215-1224,
08/15/1996
Copyright © 1996 by The American Society of Hematology
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