Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Jun 1;167(6):1909–1925. doi: 10.1084/jem.167.6.1909

Function and regulation of a murine macrophage-specific IgG Fc receptor, Fc gamma R-alpha

PMCID: PMC2189682  PMID: 2968434

Abstract

Ligand binding specificities of two cloned murine Fc gamma Rs (Fc gamma R-alpha, Fc gamma R-beta [9]) were determined by gene transfer into Fc gamma R negative cell lines. Both receptors were expressed as full- length molecules capable of IgG immune complex binding that was inhibitable by the mAb 2.4G2. The ligand binding profiles of these receptors were indistinguishable whereby both bound immune-complexed mouse IgG1, IgG2a, and IgG2b, but not IgG3. Neither receptor could bind monomeric IgG2a, indicating these receptors to be low-affinity IgG Fc receptors. Accumulation of the Fc gamma R-alpha mRNA can be induced with murine IFN-gamma at a concentration of 200 U/ml in the macrophage- like cell lines RAW 264.7 and J774a. The time course for induction indicates that the mRNA accumulation is transient but does not return to the uninduced level even after 50 h of treatment. Fc gamma R-beta mRNA was not induced by IFN-gamma, rather its expression was down modulated in mouse peritoneal macrophages. Both RAW and J774a cells lines exhibited increased receptor levels after IFN-gamma stimulation as measured by 125I-2.4G2 and ligand binding. In the absence of IFN- gamma, the RAW and J774a cell lines were minimally phagocytic, while P388D1 cells were actively phagocytic. In the presence of IFN-gamma, however, RAW 264.7 and J774a cells were induced to become actively phagocytic. Induction of Fc gamma R-alpha mRNA and protein by IFN-gamma may be part of the process by which macrophages become activated to engulf antibody-coated particles.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albino A. P., Lloyd K. O., Houghton A. N., Oettgen H. F., Old L. J. Heterogeneity in surface antigen and glycoprotein expression of cell lines derived from different melanoma metastases of the same patient. Implications for the study of tumor antigens. J Exp Med. 1981 Dec 1;154(6):1764–1778. doi: 10.1084/jem.154.6.1764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Austyn J. M., Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981 Oct;11(10):805–815. doi: 10.1002/eji.1830111013. [DOI] [PubMed] [Google Scholar]
  3. Benoist C. O., Mathis D. J., Kanter M. R., Williams V. E., 2nd, McDevitt H. O. The murine Ia alpha chains, E alpha and A alpha, show a surprising degree of sequence homology. Proc Natl Acad Sci U S A. 1983 Jan;80(2):534–538. doi: 10.1073/pnas.80.2.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. COHN Z. A., BENSON B. THE DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES. MORPHOLOGY, CYTOCHEMISTRY, AND BIOCHEMISTRY. J Exp Med. 1965 Jan 1;121:153–170. doi: 10.1084/jem.121.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang R. J., Lee S. H. Effects of interferon-gamma and tumor necrosis factor-alpha on the expression of an Ia antigen on a murine macrophage cell line. J Immunol. 1986 Nov 1;137(9):2853–2856. [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Danna K. J., Sompayrac L. M. Efficient infection of monkey cells with SV40 DNA. II. Use of low-molecular-weight DEAE-dextran for large-scale experiments. J Virol Methods. 1982 Dec;5(5-6):335–341. doi: 10.1016/0166-0934(82)90025-8. [DOI] [PubMed] [Google Scholar]
  8. Diamond B., Scharff M. D. IgG1 and IgG2b share the Fc receptor on mouse macrophages. J Immunol. 1980 Aug;125(2):631–633. [PubMed] [Google Scholar]
  9. Diamond B., Yelton D. E. A new Fc receptor on mouse macrophages binding IgG3. J Exp Med. 1981 Mar 1;153(3):514–519. doi: 10.1084/jem.153.3.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Donato N. J., Ware C. F., Byus C. V. A rat monoclonal antibody which interacts with mammalian ornithine decarboxylase at an epitope involved in phosphorylation. Biochim Biophys Acta. 1986 Nov 19;884(2):370–382. doi: 10.1016/0304-4165(86)90186-8. [DOI] [PubMed] [Google Scholar]
  11. Ezekowitz R. A., Bampton M., Gordon S. Macrophage activation selectively enhances expression of Fc receptors for IgG2a. J Exp Med. 1983 Feb 1;157(2):807–812. doi: 10.1084/jem.157.2.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fertsch D., Vogel S. N. Recombinant interferons increase macrophage Fc receptor capacity. J Immunol. 1984 May;132(5):2436–2439. [PubMed] [Google Scholar]
  13. Friedman R. L., Manly S. P., McMahon M., Kerr I. M., Stark G. R. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell. 1984 Oct;38(3):745–755. doi: 10.1016/0092-8674(84)90270-8. [DOI] [PubMed] [Google Scholar]
  14. Guyre P. M., Morganelli P. M., Miller R. Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes. J Clin Invest. 1983 Jul;72(1):393–397. doi: 10.1172/JCI110980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Heusser C. H., Anderson C. L., Grey H. M. Receptors for IgG: subclass specificity of receptors on different mouse cell types and the definition of two distinct receptors on a macrophage cell line. J Exp Med. 1977 May 1;145(5):1316–1327. doi: 10.1084/jem.145.5.1316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hogarth P. M., Hibbs M. L., Bonadonna L., Scott B. M., Witort E., Pietersz G. A., McKenzie I. F. The mouse Fc receptor for IgG (Ly-17): molecular cloning and specificity. Immunogenetics. 1987;26(3):161–168. doi: 10.1007/BF00365906. [DOI] [PubMed] [Google Scholar]
  17. Koren H. S., Handwerger B. S., Wunderlich J. R. Identification of macrophage-like characteristics in a cultured murine tumor line. J Immunol. 1975 Feb;114(2 Pt 2):894–897. [PubMed] [Google Scholar]
  18. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  19. Luster A. D., Unkeless J. C., Ravetch J. V. Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985 Jun 20;315(6021):672–676. doi: 10.1038/315672a0. [DOI] [PubMed] [Google Scholar]
  20. Markwell M. A. A new solid-state reagent to iodinate proteins. I. Conditions for the efficient labeling of antiserum. Anal Biochem. 1982 Sep 15;125(2):427–432. doi: 10.1016/0003-2697(82)90025-2. [DOI] [PubMed] [Google Scholar]
  21. Mellman I. S., Unkeless J. C. Purificaton of a functional mouse Fc receptor through the use of a monoclonal antibody. J Exp Med. 1980 Oct 1;152(4):1048–1069. doi: 10.1084/jem.152.4.1048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Miller J., Germain R. N. Efficient cell surface expression of class II MHC molecules in the absence of associated invariant chain. J Exp Med. 1986 Nov 1;164(5):1478–1489. doi: 10.1084/jem.164.5.1478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nathan C. F., Murray H. W., Cohn Z. A. The macrophage as an effector cell. N Engl J Med. 1980 Sep 11;303(11):622–626. doi: 10.1056/NEJM198009113031106. [DOI] [PubMed] [Google Scholar]
  24. Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nussenzweig M. C., Steinman R. M. Contribution of dendritic cells to stimulation of the murine syngeneic mixed leukocyte reaction. J Exp Med. 1980 May 1;151(5):1196–1212. doi: 10.1084/jem.151.5.1196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Piechaczyk M., Blanchard J. M., Marty L., Dani C., Panabieres F., El Sabouty S., Fort P., Jeanteur P. Post-transcriptional regulation of glyceraldehyde-3-phosphate-dehydrogenase gene expression in rat tissues. Nucleic Acids Res. 1984 Sep 25;12(18):6951–6963. doi: 10.1093/nar/12.18.6951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ralph P., Prichard J., Cohn M. Reticulum cell sarcoma: an effector cell in antibody-dependent cell-mediated immunity. J Immunol. 1975 Feb;114(2 Pt 2):898–905. [PubMed] [Google Scholar]
  28. Raschke W. C., Baird S., Ralph P., Nakoinz I. Functional macrophage cell lines transformed by Abelson leukemia virus. Cell. 1978 Sep;15(1):261–267. doi: 10.1016/0092-8674(78)90101-0. [DOI] [PubMed] [Google Scholar]
  29. Ravetch J. V., Luster A. D., Weinshank R., Kochan J., Pavlovec A., Portnoy D. A., Hulmes J., Pan Y. C., Unkeless J. C. Structural heterogeneity and functional domains of murine immunoglobulin G Fc receptors. Science. 1986 Nov 7;234(4777):718–725. doi: 10.1126/science.2946078. [DOI] [PubMed] [Google Scholar]
  30. Rittenberg M. B., Pratt K. L. Antitrinitrophenyl (TNP) plaque assay. Primary response of Balb/c mice to soluble and particulate immunogen. Proc Soc Exp Biol Med. 1969 Nov;132(2):575–581. doi: 10.3181/00379727-132-34264. [DOI] [PubMed] [Google Scholar]
  31. Roberts W. K., Vasil A. Evidence for the identity of murine gamma interferon and macrophage activating factor. J Interferon Res. 1982;2(4):519–532. doi: 10.1089/jir.1982.2.519. [DOI] [PubMed] [Google Scholar]
  32. Sarmiento M., Dialynas D. P., Lancki D. W., Wall K. A., Lorber M. I., Loken M. R., Fitch F. W. Cloned T lymphocytes and monoclonal antibodies as probes for cell surface molecules active in T cell-mediated cytolysis. Immunol Rev. 1982;68:135–169. doi: 10.1111/j.1600-065x.1982.tb01063.x. [DOI] [PubMed] [Google Scholar]
  33. Schreiber R. D., Pace J. L., Russell S. W., Altman A., Katz D. H. Macrophage-activating factor produced by a T cell hybridoma: physiochemical and biosynthetic resemblance to gamma-interferon. J Immunol. 1983 Aug;131(2):826–832. [PubMed] [Google Scholar]
  34. Springer T., Galfré G., Secher D. S., Milstein C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol. 1979 Apr;9(4):301–306. doi: 10.1002/eji.1830090410. [DOI] [PubMed] [Google Scholar]
  35. Steinman R. M., Nogueira N., Witmer M. D., Tydings J. D., Mellman I. S. Lymphokine enhances the expression and synthesis of Ia antigens on cultured mouse peritoneal macrophages. J Exp Med. 1980 Nov 1;152(5):1248–1261. doi: 10.1084/jem.152.5.1248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Strassmann G., Springer T. A., Adams D. O. Studies on antigens associated with the activation of murine mononuclear phagocytes: kinetics of and requirements for induction of lymphocyte function-associated (LFA)-1 antigen in vitro. J Immunol. 1985 Jul;135(1):147–151. [PubMed] [Google Scholar]
  37. Treisman R. Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5' element and c-fos 3' sequences. Cell. 1985 Oct;42(3):889–902. doi: 10.1016/0092-8674(85)90285-5. [DOI] [PubMed] [Google Scholar]
  38. Uher F., Lamers M. C., Dickler H. B. Antigen-antibody complexes bound to B-lymphocyte Fc gamma receptors regulate B-lymphocyte differentiation. Cell Immunol. 1985 Oct 15;95(2):368–379. doi: 10.1016/0008-8749(85)90324-7. [DOI] [PubMed] [Google Scholar]
  39. Unkeless J. C. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. doi: 10.1084/jem.150.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Unkeless J. C., Eisen H. N. Binding of monomeric immunoglobulins to Fc receptors of mouse macrophages. J Exp Med. 1975 Dec 1;142(6):1520–1533. doi: 10.1084/jem.142.6.1520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Weil J., Epstein C. J., Epstein L. B., Sedmak J. J., Sabran J. L., Grossberg S. E. A unique set of polypeptides is induced by gamma interferon in addition to those induced in common with alpha and beta interferons. Nature. 1983 Feb 3;301(5899):437–439. doi: 10.1038/301437a0. [DOI] [PubMed] [Google Scholar]
  42. Weinshank R. L., Luben R. A. Identification of a 150-kDa membrane component which is modulated by parathyroid hormone. Eur J Biochem. 1985 Nov 15;153(1):179–188. doi: 10.1111/j.1432-1033.1985.tb09284.x. [DOI] [PubMed] [Google Scholar]
  43. Wira C. R., Colby E. M. Regulation of secretory component by glucocorticoids in primary cultures of rat hepatocytes. J Immunol. 1985 Mar;134(3):1744–1748. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES