H-2 Antigens pp 283-296 | Cite as

Regulation of MHC Class II and Interleukin-1 Gene Expression in Differentiating Macrophages

  • Lawrence B. Schook
  • Jeffrey K. Pullen
  • Mihael J. Myers
  • Elizabeth P. Eustis-Turf
  • Xiu-Mei Wang
Part of the NATO ASI Series book series (NSSA, volume 144)


The expression and regulation of the MHC class II and interleukin-1 genes was studied during the differentiation of bone marrow stem cells into macrophages. Bone marrow cells were cultured in the presence of CSF-1 and allowed to differentiate for 3, 5, 7, and 9 d. Cells were stimulated with either medium, endotoxin (1 gg/ml) or interferon-r (IFN-r, 100 U/ml) 24 hr prior to the end of the culture period. Upon completion of culture, total cytoplasmic RNA was isolated from the adherent bone marrow-derived macrophages (BMDM) and subjected to Northern blot analysis. The A and E mRNA was constitutively expressed by medium treated BMDM after 3, g, and/d, but by 9 d the mRNA had declined to values lower than those observed on d 3. IFN-r treatment augmented A and E mRNA at each time point, whereas endotoxin treatment decreased values after 5 and 7 d. Additional studies demonstrated that IFN-r was not being produced by either the non-adherent or adherent cells nor was the production of PGE responsible for the decline in MHC class II gene expression. IL-1 mRNA was only detected in those cultures stimulated with endotoxin; medium alone or IFN-r treatment did not induce IL-1 mRNA transcription. Antigen-primed lymph node T cells and T cell hybridomas demonstrated that the ability of BMDM to function as antigen presenting cells was limited by the differentiation-specific regulation of both class II and IL-1 gene products. Exogenous Eα and Aβ genes were inserted into bone marrow stem cells using either a modified calcium phosphate transfection or an electroporation procedure and their expression was monitored using Northern blot and immunofluorescence analysis. However, there was no alteration in the expression of membrane IL-1 following trans-fection. We currently are examining the expression of regulatory factors which are responsible for the differentiation-specific regulation of MHC class II and IL-1 gene expression.


Bone Marrow Cell Northern Blot Analysis Thymidine Kinase Bone Marrow Stem Cell Nonadherent Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bancroft, G. J., Bosma, M. J., Bosma, G. C., and Unanue, E. R.: Regulation of macrophage la expression in mice with severe combined immunodeficiency: induction of la expression by a T cell-independent mechanism. J. Immunol. 137: 4 - 9, 1986.PubMedGoogle Scholar
  2. Bender, J. G., Van Epps, D. E., and Stewart, C. C.: A model for the regulation of myelopoiesis by specific factors. J. Leuk. Biol. 39: 101 - 111, 1986.Google Scholar
  3. Broxmeyer, H. E., and Dupont, B.: A role for class-II major histocompatibility complex antigens in the regulation of myelopoiesis. Prog. Allergy 36: 203 - 221, 1985.PubMedGoogle Scholar
  4. Collart, M. A., Belin, D., Vassalli, J.-D., de Kossodo, S., and Vassalli, P.: 7-Interferon enhances macrophage transcription of the tumor necro sis factor/cachectin, interleukin 1, and urokinase genes, which are controlled by short-lived repressors. J. Exp. Med. 164: 2113 - 2118, 1986.Google Scholar
  5. Eustis-Turf, E. P., Wang, X.-M., and Schook, L. B.: Electroporation of bone marrow cells: parameters and applications. Bio-Radiation, in press, 1987a.Google Scholar
  6. Eustis-Turf, E. P., Pullen, J. K., Myers, M. J., Wang, X.-M., and Schook, L. B.: Regulation of class II MHC gene expression during macrophage differentiation. In, L. B. Schook and J. G. Tew (ed.), Antigen Presenting Cells: Diversity, Differentiation, and Regulation. Alan R. Liss Publications, Inc., (in press), 1987b.Google Scholar
  7. Grabstein, K., Mochizaki, D., Kronheim, S., Price, V., Cosman, D., Urdal, D., Gillis, S., and Conlow, P.: Regulation of antibody production in vitro by granulocyte-macrophage colony stimulating factor. J. Mol. Cell. Immunol. 2:199-207, 1986.Google Scholar
  8. Ihle, J. N., and Weinstein, Y.: Immunological regulation of hematopoietic/lymphoid stem cell differentiation by interleukin-3. Adv. Immunol. 39: 1 - 50, 1986.PubMedCrossRefGoogle Scholar
  9. Kawasaki, E. S., Ladner, M. B., Wang, A. M., Van Arsdell, J., Warren, M. K., Coyne, M. Y., Schweickart, V. L., Lee, M.-T., Wilson, K. J., Boosman, A., Stanley, E. R., and David, D. F.: Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science 230: 291 - 296, 1985.Google Scholar
  10. Lee, K. C., and Wong, M.: Functional heterogeneity of culture-grown bone marrow-derived macrophages. II. Lymphokine stimulation of antigen-presenting function. J. Immunol. 128: 2487 - 2494, 1982.PubMedGoogle Scholar
  11. Metcalf, D.: The granulocyte-macrophage colony stimulating factors. Science 229: 16 - 22, 1985.PubMedCrossRefGoogle Scholar
  12. Mottram, P. L., and Miller, J. F. A. P.: Delayed-type hypersensitivity induced by antigen-pulsed, bone marrow-derived macrophages. Eur. J. Immunol. 10: 165 - 170, 1980.PubMedCrossRefGoogle Scholar
  13. Old, L. J.: Tumour necrosis factor. Polypeptide mediator network. Nature 326: 330 - 331, 1987.PubMedCrossRefGoogle Scholar
  14. Pullen, J. K., and Schook, L. B.: Bone marrow derived macrophage: Expression of endogenous and transfected class II MHC genes during differentiation. J. Immunol. 137: 1359 - 1365, 1986.PubMedGoogle Scholar
  15. Schook, L. B., Allen, P. M., and Niederhuber, J. E.: Bone marrow-derived macrophage as accessory cells in antigen-induced T cell proliferation: H-2I region requirements for L-glutamic acid60-L-alanine30-L-tyrosinel10 response. J. Immunol. 130: 661 - 664, 1983.PubMedGoogle Scholar
  16. Schook, L. B., Bingham, E. L., Gutmann, D. H., and Niederhuber, J. E.: Characterization and expression of H-2I region gene products on bone marrow-derived macrophages. Eur. J. Immunol. 12: 991 - 997, 1982.PubMedCrossRefGoogle Scholar
  17. Schook, L. B., Gutmann, D. H., Marlin, L. E., and Niederhuber, J. E.: In vitro derived bone marrow C57BL/6: expression of Ia antigens during macrophages differentiation. Transplantation 37: 585 - 590, 1984.PubMedCrossRefGoogle Scholar
  18. Stern, A. A Erb, P., and Gisler, R. H.: Ia-bearing bone marrow-cultured macrophages induce antigen-specific helper T cells for antibody synthesis. J. Immunol. 123:612-615, 1979.Google Scholar
  19. Steeg, P. S., Johnson, H. M., and Oppenheim, J. J.: Regulation of murine macrophage Ia antigen expression by an immune interferon-like lymphokine: inhibitory effect of endotoxin. J. Immunol. 129: 2402 - 2406, 1982.PubMedGoogle Scholar
  20. Tripp, C. S., Wyche, A., Unanue, E. R., and Needleman, P.: The functional significance of the regulation of macrophage la expression by endogenous arachidonate metabolites in vitro J. Immunol. 137: 3915 - 3920, 1986a.PubMedGoogle Scholar
  21. Tripp, C. S., Unanue, E. R., and Needleman, P.: Monocyte migration explains the changes in macrophage arachidonate metabolism during the immune response. Proc. Natl. Acad. Sci., U.S.A. 83: 9655 - 9659, 1986b.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Unanue, E. R., and Allen, P. M.: The basis for the immunoregulatory role of macrophage and other accessory cells. Science 236: 551 - 557, 1987.PubMedCrossRefGoogle Scholar
  23. Warren, M. K., and Ralph, P.: Macrophage growth factor CSF-1 stimulates human monocyte production of interferon, tumor necrosis factor, and colony stimulating activity. J. Immunol. 137: 2281 - 2285, 1986.PubMedGoogle Scholar
  24. Weaver, C. T., and Unanue, E. R.: T cell induction of membrane IL-1 on macrophages. J. Immunol. 137: 3868 - 3873, 1986.PubMedGoogle Scholar
  25. Wentworth, P. A., and Ziegler, H. K.: Induction of macrophage Ia expression by lipopolysaccharide and Listeria monocytogenes in congenitally athymic nude mice. J. Immunol. 138: 3167 - 3173, 1987.PubMedGoogle Scholar
  26. Ziegler, H. K., Staffileno, L. K., and Wentworth, P. Modulation of macrophage Ia-expression by lipopolysaccharide. I. Induction of Ia expression in vivo J. Immunol. 133: 1825 - 1835, 1984.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Lawrence B. Schook
    • 1
  • Jeffrey K. Pullen
    • 2
  • Mihael J. Myers
    • 1
  • Elizabeth P. Eustis-Turf
    • 1
  • Xiu-Mei Wang
    • 3
  1. 1.Laboratory of Molecular Immunology, Department of Animal SciencesUniversity of IllinoisUrbanaUSA
  2. 2.Laboratory of ImmunologyMayo ClinicRochesterUSA
  3. 3.Department of MicrobiologyInner Mongolian Medical SchoolHuhehoute, Inner MongoliaPRC

Personalised recommendations