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Cytostatic product(s) released by activated macrophages, unrelated to interleukin 1, tumor necrosis factor alpha, and

M Lepoivre1, H Boudbid, G Lemaire

  • 1U.A. CNRS 1116, Institut de Biochimie, Université de Paris-Sud, Orsay, France.

Cellular Immunology
|September 1, 1988
PubMed

Insights

Activated macrophages release cytostatic factors that inhibit DNA synthesis in EMT6 cells. These factors, with a molecular weight over 10,000 Da, are protein-based and distinct from common cytokines like IL-1, TNF-alpha, and IFN-alpha/beta.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Murine peritoneal macrophages can be activated for cytotoxic functions.
  • Activated macrophages release soluble factors that can affect target cell proliferation.

Purpose of the Study:

  • To characterize the cytostatic factor(s) released by activated macrophages.
  • To determine the nature and specificity of the anti-proliferative activity.

Main Methods:

  • Macrophage activation in vivo (trehalose dimycolate) and in vitro (lipopolysaccharide).
  • Collection and ultrafiltration of conditioned media (CM).
  • Assays for DNA synthesis inhibition in target cell lines (EMT6, P815, R-L929, KB, HT29).
  • Protease sensitivity assays and characterization of inhibitory substances.

Main Results:

  • Activated macrophages released cytostatic factor(s) in CM that completely blocked EMT6 cell DNA synthesis within 16 hours.
  • The cytostatic activity was specific, with EMT6 cells being highly sensitive, while P815 and R-L929 were less sensitive, and KB and HT29 were resistant.
  • The active factor(s) had a molecular weight greater than 10,000 Da, were destroyed by proteases, and were inhibited by products from P815 cells.
  • No correlation was found with Interleukin-1 (IL-1), Tumor Necrosis Factor alpha (TNF-alpha), or Interferon-alpha/beta (IFN-alpha/beta), as these cytokines showed minimal or no cytostatic effect on EMT6 cells.

Conclusions:

  • Activated macrophages produce potent, proteinaceous cytostatic factor(s) that selectively inhibit DNA synthesis in specific target cells.
  • The identified cytostatic activity is distinct from commonly studied cytokines like IL-1, TNF-alpha, and IFN-alpha/beta.
  • Further research is needed to identify the precise molecular nature of these novel cytostatic factors.

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