Interleukin-4 induces foreign body giant cells from human monocytes/macrophages. Differential lymphokine regulation of macrophage fusion leads to morphological variants of multinucleated giant cells.

Interleukin-4 induced the formation of foreign body-type giant multinucleated cells from human monocyte-derived macrophages, an effect that was optimized with either granulocyte-macrophage colony-stimulating factor or interleukin-3, dependent on the concentration of interleukin-4, and specifically prevented by anti-interleukin-4. Very large foreign body giant cells and, predominantly, giant cell syncytia with randomly arranged nuclei and extensive cytoplasmic spreading (285 +/- 121 nuclei and 1.151 +/- 0.303 mm2 per syncytium) were consistently obtained. Under otherwise identical culture conditions, relatively much smaller Langhans-type giant cells with circularly arranged nuclei were induced with a previously described combination of interferon-gamma plus granulocyte-macrophage colony-stimulating factor or interleukin-3 (16 +/- 6 nuclei and 0.033 +/- 0.013 mm2 per giant cell); their formation was prevented by anti-interferon-gamma but not by anti-interleukin-4. Similar rates of macrophage fusion were obtained in both culture systems (72 +/- 5% and 74 +/- 6%, respectively), but these two morphological variants did not occur simultaneously or form from one another within the 10-day culture period. These findings demonstrate that interleukin-4 is a potent human macrophage fusion factor and that differential regulation of macrophage fusion by interleukin-4 and interferon-gamma may lead to morphological variants of multinucleated giant cells.

[1]  A. Hiltner,et al.  Role for interleukin-4 in foreign-body giant cell formation on a poly(etherurethane urea) in vivo. , 1995, Journal of biomedical materials research.

[2]  J. Anderson,et al.  Complement C3 participation in monocyte adhesion to different surfaces. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[3]  M. Vadas,et al.  Interleukin 4 and human immunodeficiency virus stimulate LFA-1-ICAM-1-mediated aggregation of monocytes and subsequent giant cell formation. , 1994, The Journal of general virology.

[4]  S. Romagnani Lymphokine production by human T cells in disease states. , 1994, Annual review of immunology.

[5]  K. Suk,et al.  Regulation of murine macrophage function by IL-4: IL-4 and IFN-gamma differentially regulate macrophage tumoricidal activation. , 1993, Immunology.

[6]  S. Wahl,et al.  Suppression of monocyte function and differential regulation of IL-1 and IL-1ra by IL-4 contribute to resolution of experimental arthritis. , 1993, Journal of immunology.

[7]  K. Jones,et al.  Synovial fluid macrophages and blood monocytes differ in their response to IL-4. , 1993, Journal of immunology.

[8]  K. Ohnishi,et al.  Differential regulation of formation of multinucleated giant cells from concanavalin A-stimulated human blood monocytes by IFN-gamma and IL-4. , 1993, Journal of immunology.

[9]  J M Anderson,et al.  Theoretical analysis on cell size distribution and kinetics of foreign-body giant cell formation in vivo on polyurethane elastomers. , 1992, Journal of biomedical materials research.

[10]  A. Ferrante,et al.  IL-4 inhibits macrophage-mediated killing of Plasmodium falciparum in vitro. A possible parasite-immune evasion mechanism. , 1992, Journal of immunology.

[11]  M. Lotze,et al.  Administration of recombinant IL-4 to humans regulates gene expression, phenotype, and function in circulating monocytes. , 1992, Journal of immunology.

[12]  S. Gautam,et al.  IL-4 suppresses cytokine gene expression induced by IFN-gamma and/or IL-2 in murine peritoneal macrophages. , 1992, Journal of immunology.

[13]  L. Reinlib,et al.  Anti‐class II MHC antibody induces multinucleated giant cell formation from peripheral blood monocytes , 1992, Journal of leukocyte biology.

[14]  R. Enelow,et al.  Induction of multinucleated giant cell formation from in vitro culture of human monocytes with interleukin-3 and interferon-gamma: comparison with other stimulating factors. , 1992, American journal of respiratory cell and molecular biology.

[15]  J. Gamble,et al.  Inhibition of human monocyte adhesion by interleukin-4. , 1991, Blood.

[16]  W. Paul,et al.  Interleukin-4 : A Prototypic Immunoregulatory Lymphokine , 2003 .

[17]  J M Anderson,et al.  Foreign-body giant cells and polyurethane biostability: in vivo correlation of cell adhesion and surface cracking. , 1991, Journal of biomedical materials research.

[18]  T. Standiford,et al.  IL-4 inhibits the expression of IL-8 from stimulated human monocytes. , 1990, Journal of immunology.

[19]  J. Möst,et al.  Cytokine‐induced generation of multinucleated giant cells in vitro requires interferon‐γ and expression of LFA‐1 , 1990 .

[20]  S. Clark,et al.  Comparison of the effects of IL-3, granulocyte-macrophage colony-stimulating factor, and macrophage colony-stimulating factor in supporting monocyte differentiation in culture. Analysis of macrophage antibody-dependent cellular cytotoxicity. , 1990, Journal of immunology.

[21]  M. Fenton,et al.  Differential regulation of IL-1 production in human monocytes by IFN-gamma and IL-4. , 1990, Journal of immunology.

[22]  J. Gamble,et al.  IL-3 and granulocyte-macrophage colony-stimulating factor stimulate two distinct phases of adhesion in human monocytes. , 1990, Journal of immunology.

[23]  S. Abramson,et al.  IL-4 inhibits superoxide production by human mononuclear phagocytes. , 1990, Journal of immunology.

[24]  H. Remold,et al.  IL-4 inhibits H2O2 production and antileishmanial capacity of human cultured monocytes mediated by IFN-gamma. , 1989, Journal of immunology.

[25]  S. Douglas,et al.  Induction of multinucleated giant cell formation from human blood-derived monocytes by phorbol myristate acetate in in vitro culture. , 1989, Journal of immunology.

[26]  H. Broxmeyer,et al.  Effects of recombinant human colony stimulating factors (CSF) (granulocyte-macrophage CSF, granulocyte CSF, and CSF-1) on human monocyte/macrophage differentiation. , 1989, Journal of immunology.

[27]  D. Morton,et al.  IL-4 down-regulates IL-1 and TNF gene expression in human monocytes. , 1989, Journal of immunology.

[28]  P. Hart,et al.  Potential antiinflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J M Anderson,et al.  Inflammatory response to implants. , 1988, ASAIO transactions.

[30]  H. Radzun,et al.  Multinucleated giant cells generated in vitro. Terminally differentiated macrophages with down-regulated c-fms expression. , 1988, The American journal of pathology.

[31]  D. Rennick,et al.  Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells , 1988, The Journal of experimental medicine.

[32]  K. Smetana Multinucleate foreign-body giant cell formation. , 1987, Experimental and molecular pathology.

[33]  C. Nathan,et al.  Secretory products of macrophages. , 1987, The Journal of clinical investigation.

[34]  H. DeLuca,et al.  1 alpha,25-dihydroxyvitamin D3 promotes fusion of mouse alveolar macrophages both by a direct mechanism and by a spleen cell-mediated indirect mechanism. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[35]  B. Kraus Formation of giant cells in vivo. , 1982, Immunobiology.

[36]  T. Chambers,et al.  Inflammatory giant cells. , 1982, Immunobiology.

[37]  P. Henson,et al.  Intracellular levels and stimulated release of lysosomal enzymes from human peripheral blood monocytes and monocyte-derived macrophages. , 1980, Journal of the Reticuloendothelial Society.

[38]  W. Johnson,et al.  The separation, long-term cultivation, and maturation of the human monocyte , 1977, The Journal of experimental medicine.

[39]  L. Weiss,et al.  TRANSFORMATION OF MONOCYTES IN TISSUE CULTURE INTO MACROPHAGES, EPITHELIOID CELLS, AND MULTINUCLEATED GIANT CELLS , 1966, The Journal of cell biology.

[40]  M. Hobbs,et al.  Recombinant human y-interferon induces human monocyte polykaryon formation ( macrophage / osteoclast / hydrogen peroxide / plasminogen activator / macrophage fusion factor ) , 2022 .