RECOMBINANT HUMAN MACROPHAGE-COLONY-STIMULATING FACTOR IN NONHUMAN-PRIMATES - SELECTIVE EXPANSION OF A CD16(-KILLER-CELLS() MONOCYTE SUBSETWITH PHENOTYPIC SIMILARITY TO PRIMATE NATURAL)

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 imm unodeficiency virus infection, or metastatic malignancy, We have recen tly 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-res ponsive cynomolgus primate model to further characterize this novel mo nocyte population. Animals treated with rhM-CSF underwent a progressiv e and essentially complete conversion to the CD16(+) monocyte phenotyp e, with up to a 50-fold increase in the number of CD16(+) cells. This increase was paralleled by the emergence of a population of circulatin g cells that morphologically resembled large granular lymphocytes (LGL s). However, quantitatively, this population corresponded closely to t he number of CD16(+) monocytes, and fluorescence-activated cell sortin g (FAGS) confirmed that they were the same. In addition to their LGL-l ike morphology, many rhM-CSF-induced CD16(+) monocytes showed a patter n of size, granularity, and quantitative cell surface marker expressio n that closely resembled the pretreatment LGL/natural killer (NK) cell population but that did not resemble the pretreatment monocyte popula tion. However, rhM-CSf-induced CD16(+) monocytes could be distinguishe d from LGL/ NK cells by fact that they all expressed cell surface rece ptors for rhM-CSF, and many of them showed reduced but detectable phag ocytic and respiratory burst activity. Studies of human subjects treat ed with rhM-CSF also showed an analogous population of ''LGL-appearing '' CD16(+) mononuclear cells. Thus, our studies reveal a previously un suspected ability of cells in the monocyte lineage to adopt a phenotyp e similar to that of LGL/NK cells, The extent of this phenotypic conve rgence suggests that the two lineages retain access to elements of a s imilar developmental pathway. (C) 1996 by The American Society of Hema tology.