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J Exp Med. 1988 February 1; 167(2): 598–611.
PMCID: PMC2188835

Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells


Giant multinucleated cells (GMCs) are associated with granulomatous lesions that form in response to various infectious and noninfectious agents. The present study shows that mouse IL-4 induces the in vitro formation of GMCs by factor-dependent bone marrow and alveolar monocytes via cell fusion. GMCs appear 2 d after incubation of cell cultures with 20 U/ml or more of IL-4. Anti-IL-4 mAbs block the appearance of GMCs in these cultures, indicating that IL-4 acts directly on monocytes to promote fusion and does not secondarily induce the production of other soluble fusion factors. In soft agar cultures, IL-4 also causes the aggregation of macrophages and diminishes their migration. The role of IL-4 in a granulomatous inflammatory response is discussed.

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Selected References

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  • Papadimitriou JM, Sforsina D, Papaelias L. Kinetics of multinucleate giant cell formation and their modification by various agents in foreign body reactions. Am J Pathol. 1973 Nov;73(2):349–364. [PubMed]
  • Black MM, Epstein WL. Formation of multinucleate giant cells in organized epitheloid cell granulomas. Am J Pathol. 1974 Feb;74(2):263–274. [PubMed]
  • Sutton JS, Weiss L. Transformation of monocytes in tissue culture into macrophages, epithelioid cells, and multinucleated giant cells. An electron microscope study. J Cell Biol. 1966 Feb;28(2):303–332. [PMC free article] [PubMed]
  • Galindo B. Antigen-mediated fusion of specifically sensitized rabbit alveolar macrophages. Infect Immun. 1972 Apr;5(4):583–594. [PMC free article] [PubMed]
  • Galindo B, Lazdins J, Castillo R. Fusion of normal rabbit alveolar macrophages induced by supernatant fluids from BCG-sensitized lymph node cells after elicitation by antigen. Infect Immun. 1974 Feb;9(2):212–216. [PMC free article] [PubMed]
  • Remold HG, David RA, David JR. Characterization of migration inhibitory factor (MIF) from guinea pig lymphocytes stimulated with concanavalin A. J Immunol. 1972 Sep;109(3):578–586. [PubMed]
  • Remold HG, Mednis AD. Two migration inhibitory factors with different chromatographic behavior and isoelectric points. J Immunol. 1977 Jun;118(6):2015–2019. [PubMed]
  • Lolekha S, Dray S, Gotoff SP. Macrophage aggregation in vitro: a correlate of delayed hypersensitivity. J Immunol. 1970 Feb;104(2):296–304. [PubMed]
  • Garcia-Moreno LF, Myrvik QN. Macrophage-agglutinating factor produced in vitro by BCG-sensitized lymphocytes. Infect Immun. 1977 Sep;17(3):613–620. [PMC free article] [PubMed]
  • Nathan CF, Remold HG, David JR. Characterization of a lymphocyte factor which alters macrophage functions. J Exp Med. 1973 Feb 1;137(2):275–290. [PMC free article] [PubMed]
  • Crawford RM, Finbloom DS, Ohara J, Paul WE, Meltzer MS. B cell stimulatory factor-1 (interleukin 4) activates macrophages for increased tumoricidal activity and expression of Ia antigens. J Immunol. 1987 Jul 1;139(1):135–141. [PubMed]
  • Yokota T, Lee F, Rennick D, Hall C, Arai N, Mosmann T, Nabel G, Cantor H, Arai K. Isolation and characterization of a mouse cDNA clone that expresses mast-cell growth-factor activity in monkey cells. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1070–1074. [PubMed]
  • Lee F, Yokota T, Otsuka T, Meyerson P, Villaret D, Coffman R, Mosmann T, Rennick D, Roehm N, Smith C, et al. Isolation and characterization of a mouse interleukin cDNA clone that expresses B-cell stimulatory factor 1 activities and T-cell- and mast-cell-stimulating activities. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2061–2065. [PubMed]
  • Miyatake S, Otsuka T, Yokota T, Lee F, Arai K. Structure of the chromosomal gene for granulocyte-macrophage colony stimulating factor: comparison of the mouse and human genes. EMBO J. 1985 Oct;4(10):2561–2568. [PubMed]
  • Ohara J, Paul WE. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. [PubMed]
  • Cherwinski HM, Schumacher JH, Brown KD, Mosmann TR. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987 Nov 1;166(5):1229–1244. [PMC free article] [PubMed]
  • Rennick DM, Lee FD, Yokota T, Arai KI, Cantor H, Nabel GJ. A cloned MCGF cDNA encodes a multilineage hematopoietic growth factor: multiple activities of interleukin 3. J Immunol. 1985 Feb;134(2):910–914. [PubMed]
  • Zlotnik A, Vatter A, Hayes RL, Blumenthal E, Crowle AJ. Mouse pleural macrophages: characterization and comparison with mouse alveolar and peritoneal macrophages. J Reticuloendothel Soc. 1982 Mar;31(3):207–220. [PubMed]
  • Sone S, Bucana C, Hoyer LC, Fidler IJ. Kinetics and ultrastructural studies of the induction of rat alveolar macrophage fusion by mediators released from mitogen-stimulated lymphocytes. Am J Pathol. 1981 May;103(2):234–246. [PubMed]
  • Weinberg JB, Hobbs MM, Misukonis MA. Recombinant human gamma-interferon induces human monocyte polykaryon formation. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4554–4557. [PubMed]
  • Adams DO. The granulomatous inflammatory response. A review. Am J Pathol. 1976 Jul;84(1):164–192. [PubMed]
  • Spector WG, Willoughby DA. The origin of mononuclear cells in chronic inflammation and tuberculin reactions in the rat. J Pathol Bacteriol. 1968 Oct;96(2):389–399. [PubMed]
  • North RJ. The relative importance of blood monocytes and fixed macrophages to the expression of cell-mediated immunity to infection. J Exp Med. 1970 Sep 1;132(3):521–534. [PMC free article] [PubMed]
  • Spector WG, Reichhold N, Ryan GB. Degradation of granuloma-inducing micro-organisms by macrophages. J Pathol. 1970 Aug;101(4):339–354. [PubMed]
  • Warren KS. Hepatosplenic schistosomiasis: a great neglected disease of the liver. Gut. 1978 Jun;19(6):572–577. [PMC free article] [PubMed]
  • Williams WJ, James EM, Erasmus DA, Davies T. The fine structure of sarcoid and tuberculous granulomas. Postgrad Med J. 1970 Aug;46(538):496–500. [PMC free article] [PubMed]
  • Galindo B, Myrvik QN, Love SH. A macrophage agglutinating factor produced during a pulmonary delayed hypersensitivity reaction. J Reticuloendothel Soc. 1975 Nov;18(5):295–304. [PubMed]
  • McGregor DD, Koster FT, Mackaness GB. The short lived small lymphocyte as a mediator of cellular immunity. Nature. 1970 Nov 28;228(5274):855–856. [PubMed]
  • Ruco LP, Meltzer MS. Macrophage activation for tumor cytotoxicity: increased lymphokine responsiveness of peritoneal macrophages during acute inflammation. J Immunol. 1978 Mar;120(3):1054–1062. [PubMed]
  • Godal T, Rees RJ, Lamvik JO. Lymphocyte-mediated modification of blood-derived macrophage function in vitro; inhibition of growth of intracellular mycobacteria with lymphokines. Clin Exp Immunol. 1971 Apr;8(4):625–637. [PubMed]
  • Chambers TJ. Studies on the phagocytic capacity of macrophage polykaryons. J Pathol. 1977 Oct;123(2):65–77. [PubMed]
  • Parks DE, Weiser RS. The role of phagocytosis and natural lymphokines in the fusion of alveolar macrophages to form Langhans giant cells. J Reticuloendothel Soc. 1975 Apr;17(4):219–228. [PubMed]
  • Mariano M, Spector WG. The formation and properties of macrophage polykaryons (inflammatory giant cells). J Pathol. 1974 May;113(1):1–19. [PubMed]
  • Poste G. The tumoricidal properties of inflammatory tissue macrophages and multinucleate giant cells. Am J Pathol. 1979 Aug;96(2):595–610. [PubMed]
  • Schlesinger L, Musson RA, Johnston RB., Jr Functional and biochemical studies of multinucleated giant cells derived from the culture of human monocytes. J Exp Med. 1984 Apr 1;159(4):1289–1294. [PMC free article] [PubMed]
  • Thurman GB, Braude IA, Gray PW, Oldham RK, Stevenson HC. MIF-like activity of natural and recombinant human interferon-gamma and their neutralization by monoclonal antibody. J Immunol. 1985 Jan;134(1):305–309. [PubMed]
  • Paul WE, Ohara J. B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol. 1987;5:429–459. [PubMed]
  • Peschel C, Paul WE, Ohara J, Green I. Effects of B cell stimulatory factor-1/interleukin 4 on hematopoietic progenitor cells. Blood. 1987 Jul;70(1):254–263. [PubMed]

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