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. 1974 Nov;71(11):4273–4277. doi: 10.1073/pnas.71.11.4273

An Inhibitor of Cell Proliferation Released by Cultures of Macrophages

Jesus Calderon 1, Richard T Williams 1, Emil R Unanue 1
PMCID: PMC433864  PMID: 4216017

Abstract

Culture fluids from mouse peritoneal exudate cells inhibited [3H]thymidine incorporation by, and proliferation of, EL-4 leukemia cells, 3T3 cells, and mitogen-stimulated spleen lymphocytes. Inhibited EL-4 leukemia cells recovered their normal proliferative capacity when washed and incubated in normal medium. The inhibitory activity resided in a low-molecular-weight substance that could be absorbed by incubation with the tumor cells. This substance was dialyzable and resistant to tryptic digestion and phosphodiesterase treatment. The mononuclear phagocytes in the peritoneal exudate seemed to be the source of the inhibitor. The inhibitory material was found in the same amounts in exudates of normal mice or mice injected with peptone or infected with Listeria monocytogenes; spleen cells adherent to plastic released the inhibitor but in lesser amount. We suggest that this inhibitor may contribute to the deleterious effects found when various cells, including neoplastic ones, are cultured in the presence of macrophages.

Keywords: thymidine incorporation, leukemia cells, concanavalin A, spleen cells

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Selected References

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

  1. Bast R. C., Jr, Cleveland R. P., Littman B. H., Zbar B., Rapp H. J. Acquired cellular immunity: extracellular killing of Listeria monocytogenes by a product of immunologically activated macrophages. Cell Immunol. 1974 Feb;10(2):248–259. doi: 10.1016/0008-8749(74)90116-6. [DOI] [PubMed] [Google Scholar]
  2. Chervenick P. A., LoBuglio A. F. Human blood monocytes: stimulators of granulocyte and mononuclear colony formation in vitro. Science. 1972 Oct 13;178(4057):164–166. doi: 10.1126/science.178.4057.164. [DOI] [PubMed] [Google Scholar]
  3. Gery I., Gershon R. K., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. I. The responding cell. J Exp Med. 1972 Jul 1;136(1):128–142. doi: 10.1084/jem.136.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gery I., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediator(s). J Exp Med. 1972 Jul 1;136(1):143–155. doi: 10.1084/jem.136.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gordon S., Todd J., Cohn Z. A. In vitro synthesis and secretion of lysozyme by mononuclear phagocytes. J Exp Med. 1974 May 1;139(5):1228–1248. doi: 10.1084/jem.139.5.1228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hoffmann M., Dutton R. W. Immune response restoration with macrophage culture supernatants. Science. 1971 Jun 4;172(3987):1047–1048. doi: 10.1126/science.172.3987.1047. [DOI] [PubMed] [Google Scholar]
  7. Keller R. Cytostatic elimination of syngeneic rat tumor cells in vitro by nonspecifically activated macrophages. J Exp Med. 1973 Sep 1;138(3):625–644. doi: 10.1084/jem.138.3.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kramer J. J., Granger G. A. The in vitro induction and release of a cell toxin by immune C57B1-6 mouse peritoneal macrophages. Cell Immunol. 1972 Jan;3(1):88–100. doi: 10.1016/0008-8749(72)90229-8. [DOI] [PubMed] [Google Scholar]
  9. Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Nelson D. S. Production by stimulated macrophages of factors depressing lymphocyte transformation. Nature. 1973 Nov 30;246(5431):306–307. doi: 10.1038/246306a0. [DOI] [PubMed] [Google Scholar]
  11. Unanue E. R. The regulatory role of macrophages in antigenic stimulation. Adv Immunol. 1972;15:95–165. doi: 10.1016/s0065-2776(08)60684-7. [DOI] [PubMed] [Google Scholar]
  12. Unkeless J. C., Gordon S., Reich E. Secretion of plasminogen activator by stimulated macrophages. J Exp Med. 1974 Apr 1;139(4):834–850. doi: 10.1084/jem.139.4.834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Waldman S. R., Gottlieb A. A. Macrophage regulation of DNA synthesis in lymphoid cells: effects of a soluble factor from macrophages. Cell Immunol. 1973 Oct;9(1):142–156. doi: 10.1016/0008-8749(73)90175-5. [DOI] [PubMed] [Google Scholar]

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