Recombinant human macrophage colony-stimulating factor in nonhuman primates: Selective expansion of a CD16+ monocyte subset with phenotypic similarity to primate natural killer cells

David H. Munn, Andrea G. Bree, Arthur C. Beall, Michelle D. Kaviani, Hernan Sabio, Robert G. Schaub, R. Katherine Alpaugh, Louis M. Weiner, Samuel J. Goldman

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43 Scopus citations

Abstract

The CD16 receptor (FcγR-III) is found on many tissue macrophages (Mφs), 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.

Original languageEnglish (US)
Pages (from-to)1215-1224
Number of pages10
JournalBlood
Volume88
Issue number4
StatePublished - Aug 15 1996

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Munn, D. H., Bree, A. G., Beall, A. C., Kaviani, M. D., Sabio, H., Schaub, R. G., Alpaugh, R. K., Weiner, L. M., & Goldman, S. J. (1996). 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, 88(4), 1215-1224.