Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1982 Feb;69(2):270–276. doi: 10.1172/JCI110449

Effect of colony stimulating factor on murine macrophages. Induction of antitumor activity.

E J Wing, A Waheed, R K Shadduck, L S Nagle, K Stephenson
PMCID: PMC370975  PMID: 6799546

Abstract

Colony stimulating factor (CSF) was assessed for its capacity to stimulate antitumor activity in macrophages. Murine peritoneal macrophages incubated with CSF for 48 h inhibited [3H[thymidine (TdR) incorporation by P815 tumor cells to approximately 20% of control values. Inhibition of CSF-stimulated macrophages was significantly greater than inhibition by unstimulated macrophages (P less than 0.001). CSF had little direct effect on the proliferation of either tumor cells or macrophages alone, indicating that the antitumor activity of CSF was mediated by macrophages. it is unlikely that impurities in the CSF preparations were responsible for the effect since CSF that had been purified to homogeneity was as active as crude preparations. Furthermore the activity of CSF on macrophages was blocked by addition of purified anti-CSF antibodies. In addition to being tumoristatic, CSF-stimulated macrophages were tumoricidal as determined by a tumor colony growth assay. Tumor cells that had been incubated with CSF-stimulated macrophages showed a significant reduction in tumor colony-forming units (P less than 0.01). Thus, in addition to its effect on hemopoietic stem cells, CSF induces certain effector functions in mature macrophages that may enhance endogenous antitumor host defenses.

Full text

PDF
275

Selected References

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

  1. Hamilton J. A., Stanley E. R., Burgess A. W., Shadduck R. K. Stimulation of macrophage plasminogen activator activity by colony-stimulating factors. J Cell Physiol. 1980 Jun;103(3):435–445. doi: 10.1002/jcp.1041030309. [DOI] [PubMed] [Google Scholar]
  2. Handman E., Burgess A. W. Stimulation by granulocyte-macrophage colony-stimulating factor of Leishmania tropica killing by macrophages. J Immunol. 1979 Mar;122(3):1134–1137. [PubMed] [Google Scholar]
  3. Hibbs J. B., Jr, Lambert L. H., Jr, Remington J. S. Control of carcinogenesis: a possible role for the activated macrophage. Science. 1972 Sep 15;177(4053):998–1000. doi: 10.1126/science.177.4053.998. [DOI] [PubMed] [Google Scholar]
  4. Hibbs J. B., Jr, Lambert L. H., Jr, Remington J. S. Possible role of macrophage mediated nonspecific cytotoxicity in tumour resistance. Nat New Biol. 1972 Jan 12;235(54):48–50. doi: 10.1038/newbio235048a0. [DOI] [PubMed] [Google Scholar]
  5. Jett J. R., Mantovani A., Herberman R. B. Augmentation of human monocyte-mediated cytolysis by interferon. Cell Immunol. 1980 Sep 1;54(2):425–434. doi: 10.1016/0008-8749(80)90222-1. [DOI] [PubMed] [Google Scholar]
  6. Krahenbuhl J. L., Lambert L. H., Jr Cytokinetic studies of the effects of activated macrophages on tumor target cells. J Natl Cancer Inst. 1975 Jun;54(6):1433–1437. doi: 10.1093/jnci/54.6.1433. [DOI] [PubMed] [Google Scholar]
  7. Kurland J. I., Bockman R. S., Broxmeyer H. E., Moore M. A. Limitation of excessive myelopoiesis by the intrinsic modulation of macrophage-derived prostaglandin E. Science. 1978 Feb 3;199(4328):552–555. doi: 10.1126/science.304600. [DOI] [PubMed] [Google Scholar]
  8. Metcalf D. Regulation of granulocyte and monocyte-macrophage proliferation by colony stimulating factor (CSF): a review. Exp Hematol. 1973;1(4):185–201. [PubMed] [Google Scholar]
  9. Moore R. N., Oppenheim J. J., Farrar J. J., Carter C. S., Jr, Waheed A., Shadduck R. K. Production of lymphocyte-activating factor (Interleukin 1) by macrophages activated with colony-stimulating factors. J Immunol. 1980 Sep;125(3):1302–1305. [PubMed] [Google Scholar]
  10. Nacy C. A., Leonard E. J., Meltzer M. S. Macrophages in resistance to rickettsial infections: characterization of lymphokines that induce rickettsiacidal activity in macrophages. J Immunol. 1981 Jan;126(1):204–207. [PubMed] [Google Scholar]
  11. Schultz R. M., Papamatheakis J. D., Chirigos M. A. Interferon: an inducer of macrophage activation by polyanions. Science. 1977 Aug 12;197(4304):674–676. doi: 10.1126/science.877584. [DOI] [PubMed] [Google Scholar]
  12. Shadduck R. K., Metcalf D. Preparation and neutralization characteristics of an anti-CSF antibody. J Cell Physiol. 1975 Oct;86(2 Pt 1):247–252. doi: 10.1002/jcp.1040860208. [DOI] [PubMed] [Google Scholar]
  13. Shadduck R. K., Waheed A., Pigoli G., Boegel F., Higgins L. Fractionation of antibodies to L-cell colony-stimulating factor by affinity chromatography. Blood. 1979 Jun;53(6):1182–1190. [PubMed] [Google Scholar]
  14. Shadduck R. K., Waheed A., Porcellini A., Rizzoli V., Levin J. A method for the removal of endotoxin from purified colony-stimulating factor. Proc Soc Exp Biol Med. 1980 May;164(1):40–44. doi: 10.3181/00379727-164-40821. [DOI] [PubMed] [Google Scholar]
  15. Waheed A., Shadduck R. K. Purification and properties of L cell-derived colony-stimulating factor. J Lab Clin Med. 1979 Jul;94(1):180–193. [PubMed] [Google Scholar]
  16. Wing E. J., Gardner I. D., Ryning F. W., Remington J. S. Dissociation of effector functions in populations of activated macrophages. Nature. 1977 Aug 18;268(5621):642–644. doi: 10.1038/268642a0. [DOI] [PubMed] [Google Scholar]
  17. Wing E. J., Krahenbuhl J. L., Remington J. S. Studies of macrophage function during Trichinella spiralis infection in mice. Immunology. 1979 Mar;36(3):479–485. [PMC free article] [PubMed] [Google Scholar]
  18. Wing E. J., Remington J. S. Studies on the regulation of lymphocyte reactivity by normal and activated macrophages. Cell Immunol. 1977 Apr;30(1):108–121. doi: 10.1016/0008-8749(77)90052-1. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES