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.
Full Text
The Full Text of this article is available as a PDF (1.0 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abramson S. L., Gallin J. I. IL-4 inhibits superoxide production by human mononuclear phagocytes. J Immunol. 1990 Jan 15;144(2):625–630. [PubMed] [Google Scholar]
- Cao H., Wolff R. G., Meltzer M. S., Crawford R. M. 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] [Google Scholar]
- Crawford R. M., Finbloom D. S., Ohara J., Paul W. E., Meltzer M. S. 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] [Google Scholar]
- 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. doi: 10.1073/pnas.85.17.6232. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Donnelly R. P., Fenton M. J., Finbloom D. S., Gerrard T. L. 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] [Google Scholar]
- Fauve R. M., Jusforgues H., Hevin B. Maintenance of granuloma macrophages in serum-free medium. J Immunol Methods. 1983 Nov 25;64(3):345–351. doi: 10.1016/0022-1759(83)90442-8. [DOI] [PubMed] [Google Scholar]
- Gerrard T. L., Dyer D. R., Mostowski H. S. 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] [Google Scholar]
- Hart P. H., Whitty G. A., Burgess D. R., Croatto M., Hamilton J. A. Augmentation of glucocorticoid action on human monocytes by interleukin-4. Lymphokine Res. 1990 Summer;9(2):147–153. [PubMed] [Google Scholar]
- Lauener R. P., Goyert S. M., Geha R. S., Vercelli D. Interleukin 4 down-regulates the expression of CD14 in normal human monocytes. Eur J Immunol. 1990 Nov;20(11):2375–2381. doi: 10.1002/eji.1830201103. [DOI] [PubMed] [Google Scholar]
- McBride W. H., Economou J. S., 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] [Google Scholar]
- Pennica D., Hayflick J. S., Bringman T. S., Palladino M. A., Goeddel D. V. 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. doi: 10.1073/pnas.82.18.6060. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Phillips W. A., Croatto M., Hamilton J. A. Priming the macrophage respiratory burst with IL-4: enhancement with TNF-alpha but inhibition by IFN-gamma. Immunology. 1990 Aug;70(4):498–503. [PMC free article] [PubMed] [Google Scholar]
- Schreiber S., Blum J. S., Stenson W. F., MacDermott R. P., Stahl P. D., Teitelbaum S. L., Perkins S. L. 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. doi: 10.1073/pnas.88.5.1616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Snapper C. M., Paul W. E. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987 May 22;236(4804):944–947. doi: 10.1126/science.3107127. [DOI] [PubMed] [Google Scholar]
- Stahl P. D. The macrophage mannose receptor: current status. Am J Respir Cell Mol Biol. 1990 Apr;2(4):317–318. doi: 10.1165/ajrcmb/2.4.317. [DOI] [PubMed] [Google Scholar]
- Stahl P., Schlesinger P. H., Sigardson E., Rodman J. S., Lee Y. C. Receptor-mediated pinocytosis of mannose glycoconjugates by macrophages: characterization and evidence for receptor recycling. Cell. 1980 Jan;19(1):207–215. doi: 10.1016/0092-8674(80)90402-x. [DOI] [PubMed] [Google Scholar]
- Standiford T. J., Strieter R. M., Chensue S. W., Westwick J., Kasahara K., Kunkel S. L. IL-4 inhibits the expression of IL-8 from stimulated human monocytes. J Immunol. 1990 Sep 1;145(5):1435–1439. [PubMed] [Google Scholar]
- Tan H. P., Nehlsen-Cannarella S. L., Garberoglio C. A., Tosk J. M. Recombinant interleukin-4 enhances the chemiluminescent oxidative burst of murine peritoneal macrophages. J Leukoc Biol. 1991 Jun;49(6):587–591. doi: 10.1002/jlb.49.6.587. [DOI] [PubMed] [Google Scholar]
- te Velde A. A., Klomp J. P., Yard B. A., de Vries J. E., Figdor C. G. Modulation of phenotypic and functional properties of human peripheral blood monocytes by IL-4. J Immunol. 1988 Mar 1;140(5):1548–1554. [PubMed] [Google Scholar]