title: Recombinant human macrophage colony-stimulating factor in nonhuman primates: selective expansion of a CD16+ monocyte subset with phenotypic similarity to primate natural killer cells.
abstract: 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.
authors.affiliation: Division of Pediatric Hematology-Oncology, Medical College of Georgia, Augusta, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Munn
authors.forename: A G
authors.initials: AG
authors.lastname: Bree
authors.forename: A C
authors.initials: AC
authors.lastname: Beall
authors.forename: M D
authors.initials: MD
authors.lastname: Kaviani
authors.forename: H
authors.initials: H
authors.lastname: Sabio
authors.forename: R G
authors.initials: RG
authors.lastname: Schaub
authors.forename: R K
authors.initials: RK
authors.lastname: Alpaugh
authors.forename: L M
authors.initials: LM
authors.lastname: Weiner
authors.forename: S J
authors.initials: SJ
authors.lastname: Goldman
mesh_terms: D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis*; D019002:CD56 Antigen / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology*; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008252:Macaca fascicularis; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D010587:Phagocytosis; D017452:Receptors, IgG / Q000032:analysis; D011994:Recombinant Proteins; D016897:Respiratory Burst
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D019002:CD56 Antigen; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor