Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1984 Aug;45(2):417–423. doi: 10.1128/iai.45.2.417-423.1984

Endogenous interferon production by endotoxin-responsive macrophages provides an autostimulatory differentiation signal.

S N Vogel, D Fertsch
PMCID: PMC263243  PMID: 6378797

Abstract

Previous studies have demonstrated that peritoneal macrophages (resident or thioglycolate-induced) derived from mouse strains fully responsive to gram-negative endotoxins continue to differentiate in vitro, as evidenced by an increased capacity to phagocytose via the Fc receptor with time in culture. In contrast, macrophages derived from endotoxin-hyporesponsive mouse strains (e.g., C3H/HeJ or C57BL/10ScN) exhibit no such increase in phagocytic capacity, and, in fact, significantly lose the capacity to phagocytose particles opsonized with immunoglobulin G with time in culture. This defect was found to be fully correctable by the addition to the cultures of an exogenous source of alpha, beta, or gamma interferon. In this study, we compared C3H/HeN (endotoxin-responsive) and C3H/HeJ (endotoxin-responsive) and C3H/HeJ (endotoxin-hyporesponsive) macrophages in an attempt to elucidate the mechanism responsible for this difference in phagocytic (differentiative) potential. The following observations support the hypothesis that endotoxin-responsive macrophages, in contrast to endotoxin-hyporesponsive macrophages, produce significantly higher levels of an autostimulatory differentiation signal that appears to be macrophage-derived interferon. (i) Anti-alpha/beta-interferon antibody greatly reduces the ability of C3H/HeN macrophages to phagocytose opsonized erythrocytes: (ii) C3H/HeJ macrophages can be made more phagocytic by coculture with C3H/HeN macrophages or by treatment with supernatants derived from C3H/HeN macrophage cultures; and (iii) C3H/HeN macrophages spontaneously lose Mac-1 antigen with time in culture. C3H/HeJ macrophages must be interferon-treated to be equivalently down-regulated.

Full text

PDF
417

Selected References

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

  1. Bianco C., Griffin F. M., Jr, Silverstein S. C. Studies of the macrophage complement receptor. Alteration of receptor function upon macrophage activation. J Exp Med. 1975 Jun 1;141(6):1278–1290. doi: 10.1084/jem.141.6.1278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cohn Z. A. Activation of mononuclear phagocytes: fact, fancy, and future. J Immunol. 1978 Sep;121(3):813–816. [PubMed] [Google Scholar]
  3. Glode L. M., Rosenstreich D. L. Genetic control of B cell activation by bacterial lipopolysaccharide is mediated by multiple distinct genes or alleles. J Immunol. 1976 Dec;117(6):2061–2066. [PubMed] [Google Scholar]
  4. Hibbs J. B., Jr, Taintor R. R., Chapman H. A., Jr, Weinberg J. B. Macrophage tumor killing: influence of the local environment. Science. 1977 Jul 15;197(4300):279–282. doi: 10.1126/science.327547. [DOI] [PubMed] [Google Scholar]
  5. Moore R. N., Larsen H. S., Horohov D. W., Rouse B. T. Endogenous regulation of macrophage proliferative expansion by colony-stimulating factor-induced interferon. Science. 1984 Jan 13;223(4632):178–181. doi: 10.1126/science.6606850. [DOI] [PubMed] [Google Scholar]
  6. Nowakowski M., Edelson P. J., Bianco C. Activation of C3H/HeJ macrophages by endotoxin. J Immunol. 1980 Nov;125(5):2189–2194. [PubMed] [Google Scholar]
  7. Pace J. L., Russell S. W., Torres B. A., Johnson H. M., Gray P. W. Recombinant mouse gamma interferon induces the priming step in macrophage activation for tumor cell killing. J Immunol. 1983 May;130(5):2011–2013. [PubMed] [Google Scholar]
  8. Rosenstreich D. L., Vogel S. N., Jacques A. R., Wahl L. M., Oppenheim J. J. Macrophage sensitivity to endotoxin: genetic control by a single codominant gene. J Immunol. 1978 Nov;121(5):1664–1670. [PubMed] [Google Scholar]
  9. Ruco L. P., Meltzer M. S. Defective tumoricidal capacity of macrophages from C3H/HeJ mice. J Immunol. 1978 Jan;120(1):329–334. [PubMed] [Google Scholar]
  10. Ryan J. L., McAdam K. P. Genetic non-responsiveness of murine fibroblasts to bacterial endotoxin. Nature. 1977 Sep 8;269(5624):153–155. doi: 10.1038/269153a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Sultzer B. M. Genetic analysis of lymphocyte activation by lipopolysaccharide Endotoxin. Infect Immun. 1976 Jun;13(6):1579–1584. doi: 10.1128/iai.13.6.1579-1584.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sultzer B. M. Genetic control of host responses to endotoxin. Infect Immun. 1972 Jan;5(1):107–113. doi: 10.1128/iai.5.1.107-113.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Vogel S. N., English K. E., Fertsch D., Fultz M. J. Differential modulation of macrophage membrane markers by interferon: analysis of Fc and C3b receptors, Mac-1 and Ia antigen expression. J Interferon Res. 1983;3(2):153–160. doi: 10.1089/jir.1983.3.153. [DOI] [PubMed] [Google Scholar]
  15. Vogel S. N., English K. E., O'Brien A. D. Silica enhancement of murine endotoxin sensitivity. Infect Immun. 1982 Nov;38(2):681–685. doi: 10.1128/iai.38.2.681-685.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Vogel S. N., Finbloom D. S., English K. E., Rosenstreich D. L., Langreth S. G. Interferon-induced enhancement of macrophage Fc receptor expression: beta-interferon treatment of C3H/HeJ macrophages results in increased numbers and density of Fc receptors. J Immunol. 1983 Mar;130(3):1210–1214. [PubMed] [Google Scholar]
  17. Vogel S. N., Hilfiker M. L., Caulfield M. J. Endotoxin-induced T lymphocyte proliferation. J Immunol. 1983 Apr;130(4):1774–1779. [PubMed] [Google Scholar]
  18. Vogel S. N., Rosenstreich D. L. Defective Fc receptor-mediated phagocytosis in C3H/HeJ macrophages. I. Correction by lymphokine-induced stimulation. J Immunol. 1979 Dec;123(6):2842–2850. [PubMed] [Google Scholar]
  19. Vogel S. N., Weedon L. L., Moore R. N., Rosenstreich D. L. Correction of defective macrophage differentiation in C3H/HeJ mice by an interferon-like molecule. J Immunol. 1982 Jan;128(1):380–387. [PubMed] [Google Scholar]
  20. Watson J., Kelly K., Largen M., Taylor B. A. The genetic mapping of a defective LPS response gene in C3H/HeJ mice. J Immunol. 1978 Feb;120(2):422–424. [PubMed] [Google Scholar]
  21. Watson J., Largen M., McAdam K. P. Genetic control of endotoxic responses in mice. J Exp Med. 1978 Jan 1;147(1):39–49. doi: 10.1084/jem.147.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Weinberg J. B., Chapman H. A., Jr, Hibbs J. B., Jr Characterization of the effects of endotoxin on macrophage tumor cell killing. J Immunol. 1978 Jul;121(1):72–80. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES