Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
Recombinant human macrophage colony-stimulating factor in nonhuman primates: selective expansion of a CD16+ monocyte subset with phenotypic similarity to primate natural killer cells.
Blood. 1996 Aug 15;88(4):1215-24. Unique Identifier : AIDSLINE MED/96329554 Munn DH; Bree AG; Beall AC; Kaviani MD; Sabio H; Schaub RG; Alpaugh RK; Weiner LM; Goldman SJ; Division of Pediatric Hematology-Oncology, Medical College of; Georgia, Augusta, USA.
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.
Keywords: Animal Antigens, CD14/ANALYSIS Antigens, CD56/ANALYSIS Antigens, Differentiation, Myelomonocytic/*ANALYSIS Flow Cytometry Human Immunophenotyping Killer Cells, Natural/*CYTOLOGY Macaca fascicularis Macrophage Colony-Stimulating Factor/*PHARMACOLOGY Male Monocytes/*CYTOLOGY/IMMUNOLOGY Phagocytosis Receptors, IgG/ANALYSIS Recombinant Proteins Respiratory Burst Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE 961130
M96B1872
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Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
