Generation of multinucleated giant cells by culture of monocyte-derived macrophages with IL-4.
Culturing human monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) has been reported to provoke the formation of multinucleated giant cells (GCs). In the present work, GCs were generated in a two-step procedure in which macrophages were first differentiated from monocytes before being fused into GCs. The two cytokines used acted sequentially. GM-CSF was required for monocyte differentiation and IL-4 for macrophage fusion. Macrophages were purified from cultures of blood mononuclear cells maintained for 7 days in plastic bags. When seeded in conventional plastic-ware in the presence of IL-4, these macrophages showed an increased motility, spread in thin cytoplasmic lamellas, regrouped in clusters, and within 1-3 weeks, differentiated into GCs. Multinucleated cells also appeared in IL-4-untreated macrophage cultures but the number of nuclei did not exceed 2 or 3, compared with more than 30 in the presence of IL-4. Scanning electron microscopy of GCs showed highly developed pseudopods. GCs reacted with anti-CD11b, -CD54, -CD68, -HLA-ABC, and -HLA-DR monoclonal antibodies and AMH-152 but were CD14- and CD64-negative. Both untreated and IL-4-treated macrophages conserved pinocytic and phagocytic activity. Thus, IL-4 induced a differentiation process in which macrophages lost markers like CD14 and CD64, acquired an enhanced membrane motility, and fused in multinucleated GCs.
Dugast
C
C
Département de Biologie, Centre Régional de Lutte Contre le Cancer, Rennes, France.
Gaudin
A
A
Toujas
L
L
D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015726:Giant Cells / Q000166:cytology* / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype
D000954:Antigens, Surface; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor