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J Exp Med. 1992 July 1; 176(1): 287–292.
PMCID: PMC2119288

Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation

Abstract

Expression of the macrophage mannose receptor is inhibited by interferon gamma (IFN-gamma), a T helper type 1 (Th-1)-derived lymphokine. Interleukin 4 (IL-4), a Th-2 lymphocyte product, upregulates major histocompatibility class II antigen expression but inhibits inflammatory cytokine production by macrophages. We have studied the effect of IL-4 on expression of the macrophage mannose receptor (MMR) by elicited peritoneal macrophages. We found that recombinant murine IL-4 enhances MMR surface expression (10-fold) and activity (15-fold), as measured by the respective binding and degradation of 125I-mannose-bovine serum albumin. Polymerase chain reaction analysis of cDNAs from purified primary macrophage populations revealed that MMR, but not lysozyme or tumor necrosis factor alpha, mRNA levels were markedly increased by IL-4. The above effects were associated with morphologic changes. These data establish IL-4 as a potent and selective enhancer of murine MMR activity in vitro. IL-4 induces inflammatory macrophages to adopt an alternative activation phenotype, distinct from that induced by IFN-gamma, characterized by a high capacity for endocytic clearance of mannosylated ligands, enhanced (albeit restricted) MHC class II antigen expression, and reduced proinflammatory cytokine secretion.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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]
  • Gerrard TL, Dyer DR, Mostowski HS. IL-4 and granulocyte-macrophage colony-stimulating factor selectively increase HLA-DR and HLA-DP antigens but not HLA-DQ antigens on human monocytes. J Immunol. 1990 Jun 15;144(12):4670–4674. [PubMed]
  • Cao H, Wolff RG, Meltzer MS, Crawford RM. Differential regulation of class II MHC determinants on macrophages by IFN-gamma and IL-4. J Immunol. 1989 Dec 1;143(11):3524–3531. [PubMed]
  • te Velde AA, Klomp JP, Yard BA, de Vries JE, Figdor CG. Modulation of phenotypic and functional properties of human peripheral blood monocytes by IL-4. J Immunol. 1988 Mar 1;140(5):1548–1554. [PubMed]
  • Donnelly RP, Fenton MJ, Finbloom DS, Gerrard TL. Differential regulation of IL-1 production in human monocytes by IFN-gamma and IL-4. J Immunol. 1990 Jul 15;145(2):569–575. [PubMed]
  • McBride WH, Economou JS, Nayersina R, Comora S, Essner R. Influences of interleukins 2 and 4 on tumor necrosis factor production by murine mononuclear phagocytes. Cancer Res. 1990 May 15;50(10):2949–2952. [PubMed]
  • Standiford TJ, Strieter RM, Chensue SW, Westwick J, Kasahara K, Kunkel SL. IL-4 inhibits the expression of IL-8 from stimulated human monocytes. J Immunol. 1990 Sep 1;145(5):1435–1439. [PubMed]
  • Hart PH, Whitty GA, Burgess DR, Croatto M, Hamilton JA. Augmentation of glucocorticoid action on human monocytes by interleukin-4. Lymphokine Res. 1990 Summer;9(2):147–153. [PubMed]
  • Abramson SL, Gallin JI. IL-4 inhibits superoxide production by human mononuclear phagocytes. J Immunol. 1990 Jan 15;144(2):625–630. [PubMed]
  • Phillips WA, Croatto M, Hamilton JA. Priming the macrophage respiratory burst with IL-4: enhancement with TNF-alpha but inhibition by IFN-gamma. Immunology. 1990 Aug;70(4):498–503. [PubMed]
  • Tan HP, Nehlsen-Cannarella SL, Garberoglio CA, Tosk JM. Recombinant interleukin-4 enhances the chemiluminescent oxidative burst of murine peritoneal macrophages. J Leukoc Biol. 1991 Jun;49(6):587–591. [PubMed]
  • Fauve RM, Jusforgues H, Hevin B. Maintenance of granuloma macrophages in serum-free medium. J Immunol Methods. 1983 Nov 25;64(3):345–351. [PubMed]
  • Stahl P, Schlesinger PH, Sigardson E, Rodman JS, Lee YC. Receptor-mediated pinocytosis of mannose glycoconjugates by macrophages: characterization and evidence for receptor recycling. Cell. 1980 Jan;19(1):207–215. [PubMed]
  • Pennica D, Hayflick JS, Bringman TS, Palladino MA, Goeddel DV. Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6060–6064. [PubMed]
  • Cross M, Mangelsdorf I, Wedel A, Renkawitz R. Mouse lysozyme M gene: isolation, characterization, and expression studies. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6232–6236. [PubMed]
  • Lauener RP, Goyert SM, Geha RS, Vercelli D. Interleukin 4 down-regulates the expression of CD14 in normal human monocytes. Eur J Immunol. 1990 Nov;20(11):2375–2381. [PubMed]
  • Stahl PD. The macrophage mannose receptor: current status. Am J Respir Cell Mol Biol. 1990 Apr;2(4):317–318. [PubMed]
  • Schreiber S, Blum JS, Stenson WF, MacDermott RP, Stahl PD, Teitelbaum SL, Perkins SL. Monomeric IgG2a promotes maturation of bone-marrow macrophages and expression of the mannose receptor. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1616–1620. [PubMed]
  • Snapper CM, Paul WE. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987 May 22;236(4804):944–947. [PubMed]

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