title: Induction of multinucleated giant cell formation from in vitro culture of human monocytes with interleukin-3 and interferon-gamma: comparison with other stimulating factors.
abstract: One of the hallmarks of the granulomatous response to infection is the formation of multinucleated giant cells (MGC.) In an effort to study MGC, we examined the fusion-promoting effects of a variety of stimulating factors on human peripheral blood monocytes cultured on plastic surfaces in serum-supplemented media. MGC formation was minimally to moderately enhanced by interferon-gamma (IFN-gamma), interleukin (IL)-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), retinoic acid (RA), and IL-6. IL-4 (which has been reported to promote MGC formation from murine macrophages) had an inhibitory effect. IFN-gamma was not required for MGC formation but it significantly increased the fusion-promoting activity of GM-CSF, 1,25-(OH)2D3, RA, and IL-6, IL-3, a hematopoietic growth factor, has been recently shown to induce osteoclast formation from murine bone marrow mononuclear cells. The most striking effect was seen with the combination of IL-3 and IFN-gamma. Fusion index is defined as a percentage of nuclei found within MGC, and an index of 67% at 1 wk was found. The formation of some very large cells with 50 to 100 nuclei was noted. Both Langhans' and foreign-body type cells were seen. Transmission electron micrographs clearly demonstrate the absence of plasma membrane between nuclei. Induction of MGC from peripheral human blood monocytes by IL-3 and IFN-gamma provides an in vitro system for the study of the formation and function of these cells.
authors.affiliation: Department of Medicine, University of Virginia School of Medicine, Charlottesville 22908.
authors.forename: R I
authors.initials: RI
authors.lastname: Enelow
authors.forename: G W
authors.initials: GW
authors.lastname: Sullivan
authors.forename: H T
authors.initials: HT
authors.lastname: Carper
authors.forename: G L
authors.initials: GL
authors.lastname: Mandell
mesh_terms: D002459:Cell Fusion; D002478:Cells, Cultured; D004357:Drug Synergism; D015726:Giant Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D006133:Growth Substances; D007377:Interleukin-3; D007371:Interferon-gamma