Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1976 Mar 1;143(3):631–647. doi: 10.1084/jem.143.3.631

Factors regulating macrophage production and growth: identity of colony- stimulating factor and macrophage growth factor

PMCID: PMC2190132  PMID: 1082493

Abstract

The activities of a colony-stimulating factor (CSF), which stimulates granulocyte-macrophage colony formation by mouse hemopoietic cells, and macrophage growth factor (MGF), which stimulates proliferation of activated peritoneal macrophages, have been demonstrated by various criteria to reside in the same molecular species. These criteria include occurrence in various sources and copurification of the activities in mouse L-cell-conditioned medium as well as the biological, physicochemical, and antigenic properties of the activities of L-cell-conditioned medium. CSF and MGF activities of L-cell- conditioned medium are ascribable to a glycoprotein of mol wt approximately 60,000 which migrates electrophoretically with alpha- globulin. Human urinary CSF, which also possesses MGF activity, has similar properties and can be neutralized by antiserum to highly purified L-cell medium CSF. A procedure is described for the partial purification of material from L-cell medium that has activity at 1 ng/ml in both MGF and CSF assays.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

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

  1. Amano T., Richelson E., Nirenberg M. Neurotransmitter synthesis by neuroblastoma clones (neuroblast differentiation-cell culture-choline acetyltransferase-acetylcholinesterase-tyrosine hydroxylase-axons-dendrites). Proc Natl Acad Sci U S A. 1972 Jan;69(1):258–263. doi: 10.1073/pnas.69.1.258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aspberg K., Porath J. Group-specific adsorption of glycoproteins. Acta Chem Scand. 1970;24(5):1839–1841. doi: 10.3891/acta.chem.scand.24-1839. [DOI] [PubMed] [Google Scholar]
  3. Austin P. E., McCulloch E. A., Till J. E. Characterization of the factor in L-cell conditioned medium capable of stimulating colony formation by mouse marrow cells in culture. J Cell Physiol. 1971 Apr;77(2):121–134. doi: 10.1002/jcp.1040770202. [DOI] [PubMed] [Google Scholar]
  4. Bradley T. R., Metcalf D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1966 Jun;44(3):287–299. doi: 10.1038/icb.1966.28. [DOI] [PubMed] [Google Scholar]
  5. Bradley T. R., Stanley E. R., Sumner M. A. Factors from mouse tissues stimulating colony growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1971 Dec;49(6):595–603. doi: 10.1038/icb.1971.65. [DOI] [PubMed] [Google Scholar]
  6. Bradley T. R., Sumner M. A. Stimulation of mouse bone marrow colony growth in vitro by conditioned medium. Aust J Exp Biol Med Sci. 1968 Oct;46(5):607–618. doi: 10.1038/icb.1968.167. [DOI] [PubMed] [Google Scholar]
  7. Chrambach A., Reisfeld R. A., Wyckoff M., Zaccari J. A procedure for rapid and sensitive staining of protein fractionated by polyacrylamide gel electrophoresis. Anal Biochem. 1967 Jul;20(1):150–154. doi: 10.1016/0003-2697(67)90272-2. [DOI] [PubMed] [Google Scholar]
  8. Cifone M., Defendi V. Cyclic expression of a growth conditioning factor (MGF) on the cell surface. Nature. 1974 Nov 8;252(5479):151–153. doi: 10.1038/252151a0. [DOI] [PubMed] [Google Scholar]
  9. DAVIS B. J. DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964 Dec 28;121:404–427. doi: 10.1111/j.1749-6632.1964.tb14213.x. [DOI] [PubMed] [Google Scholar]
  10. Eagle H. Buffer combinations for mammalian cell culture. Science. 1971 Oct 29;174(4008):500–503. doi: 10.1126/science.174.4008.500. [DOI] [PubMed] [Google Scholar]
  11. Eaves A. C., Bruce W. R. In vitro production of colony-stimulating activity. I. Exposure of mouse peritoneal cells to endotoxin. Cell Tissue Kinet. 1974 Jan;7(1):19–30. doi: 10.1111/j.1365-2184.1974.tb00395.x. [DOI] [PubMed] [Google Scholar]
  12. FISCHER G. A. Studies of the culture of leukemic cells in vitro. Ann N Y Acad Sci. 1958 Dec 5;76(3):673–680. doi: 10.1111/j.1749-6632.1958.tb54884.x. [DOI] [PubMed] [Google Scholar]
  13. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Lin H. S., Stewart C. C. Peritoneal exudate cells. I. Growth requirement of cells capable of forming colonies in soft agar. J Cell Physiol. 1974 Jun;83(3):369–378. doi: 10.1002/jcp.1040830307. [DOI] [PubMed] [Google Scholar]
  16. Lin H., Stewart C. C. Colony formation by mouse peritoneal exudate cells in vitro. Nat New Biol. 1973 Jun 6;243(127):176–177. doi: 10.1038/newbio243176a0. [DOI] [PubMed] [Google Scholar]
  17. Margolis J., Kenrick K. G. Polyacrylamide gel electrophoresis in a continuous molecular sieve gradient. Anal Biochem. 1968 Oct 24;25(1):347–362. doi: 10.1016/0003-2697(68)90109-7. [DOI] [PubMed] [Google Scholar]
  18. Mauel J., Defendi V. Infection and transformation of mouse peritoneal macrophages by simian virus 40. J Exp Med. 1971 Aug 1;134(2):335–350. doi: 10.1084/jem.134.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mauel J., Defendi V. Regulation of DNA synthesis in mouse macrophages. I. Sources, action and purification of the macrophage growing factor (MGF). Exp Cell Res. 1971 Mar;65(1):33–42. doi: 10.1016/s0014-4827(71)80047-2. [DOI] [PubMed] [Google Scholar]
  20. Mauel J., Defendi V. Regulation of DNA synthesis in mouse macrophages. II. Studies on mechanisms of action of the macrophage growth factor. Exp Cell Res. 1971 Apr;65(2):377–385. doi: 10.1016/0014-4827(71)90016-4. [DOI] [PubMed] [Google Scholar]
  21. McNeil T. A. Release of bone marrow colony stimulating activity during immunological reactions in vitro. Nat New Biol. 1973 Aug 8;244(136):175–176. [PubMed] [Google Scholar]
  22. Metcalf D. Acute antigen-induced elevation of serum colony stimulating factor (CFS) levels. Immunology. 1971 Sep;21(3):427–436. [PMC free article] [PubMed] [Google Scholar]
  23. Metcalf D., Parker J., Chester H. M., Kincade P. W. Formation of eosinophilic-like granulocytic colonies by mouse bone marrow cells in vitro. J Cell Physiol. 1974 Oct;84(2):275–289. doi: 10.1002/jcp.1040840214. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Metcalf D. Studies on colony formation in vitro by mouse bone marrow cells. I. Continuous cluster formation and relation of clusters to colonies. J Cell Physiol. 1969 Dec;74(3):323–332. doi: 10.1002/jcp.1040740313. [DOI] [PubMed] [Google Scholar]
  26. Metcalf D. Studies on colony formation in vitro by mouse bone marrow cells. II. Action of colony stimulating factor. J Cell Physiol. 1970 Aug;76(1):89–99. doi: 10.1002/jcp.1040760113. [DOI] [PubMed] [Google Scholar]
  27. Parker J. W., Metcalf D. Production of colony-stimulating factor in mitogen-stimulated lymphocyte cultures. J Immunol. 1974 Feb;112(2):502–510. [PubMed] [Google Scholar]
  28. Parker J. W., Metcalf D. Production of colony-stimulating factor in mixed leucocyte cultures. Immunology. 1974 May;26(5):1039–1049. [PMC free article] [PubMed] [Google Scholar]
  29. Pluznik D. H., Sachs L. The cloning of normal "mast" cells in tissue culture. J Cell Physiol. 1965 Dec;66(3):319–324. doi: 10.1002/jcp.1030660309. [DOI] [PubMed] [Google Scholar]
  30. Price G. B., McCulloch E. A., Till J. E. A new human low molecular weight granulocyte colony stimulating activity. Blood. 1973 Sep;42(3):341–348. [PubMed] [Google Scholar]
  31. Price G. B., Senn J. S., McCulloch E. A., Till J. E. Heterogeneity of molecules with low molecular weight isolated from media conditioned by human leukocytes and capable of stimulating colony formation by human granulopoietic progenitor cells. J Cell Physiol. 1974 Dec;84(3):383–396. doi: 10.1002/jcp.1040840307. [DOI] [PubMed] [Google Scholar]
  32. Price G. B., Senn J. S., McCulloch E. A., Till J. E. The isolation and properties of granulocytic colony-stimulating activities from medium conditioned by human peripheral leucocytes. Biochem J. 1975 May;148(2):209–217. doi: 10.1042/bj1480209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sheridan J. W., Metcalf D. A low molecular weight factor in lung-conditioned medium stimulating granulocyte and monocyte colony formation in vitro. J Cell Physiol. 1973 Feb;81(1):11–23. doi: 10.1002/jcp.1040810103. [DOI] [PubMed] [Google Scholar]
  34. Sheridan J. W., Metcalf D. Purification of mouse lung-conditioned medium colony stimulating factor (CSF). Proc Soc Exp Biol Med. 1974 May;146(1):218–221. doi: 10.3181/00379727-146-38073. [DOI] [PubMed] [Google Scholar]
  35. Sheridan J. W., Metcalf D., Stanley E. R. Further studies on the factor in lung-conditioned medium stimulating granulocyte and monocyte colony formation in vitro. J Cell Physiol. 1974 Aug;84(1):147–158. doi: 10.1002/jcp.1040840117. [DOI] [PubMed] [Google Scholar]
  36. Soderland S. C., Naum Y. Letter: Growth of pulmonary alveolar macrophages in vitro. Nature. 1973 Sep 21;245(5421):150–152. doi: 10.1038/245150a0. [DOI] [PubMed] [Google Scholar]
  37. Stanley E. R., Bradley T. R., Sumner M. A. Properties of the mouse embryo conditioned medium factor(s) stimulationg colony formation by mouse bone marrow cells grown in vitro. J Cell Physiol. 1971 Oct;78(2):301–317. doi: 10.1002/jcp.1040780219. [DOI] [PubMed] [Google Scholar]
  38. Stanley E. R., Hansen G., Woodcock J., Metcalf D. Colony stimulating factor and the regulation of granulopoiesis and macrophage production. Fed Proc. 1975 Dec;34(13):2272–2278. [PubMed] [Google Scholar]
  39. Stanley E. R., Metcalf D. Enzyme treatment of colony stimulating factor: evidence for a peptide component. Aust J Exp Biol Med Sci. 1971 Jun;49(3):281–290. doi: 10.1038/icb.1971.28. [DOI] [PubMed] [Google Scholar]
  40. Stanley E. R., Metcalf D. Partial purification and some properties of the factor in normal and leukaemic human urine stimulating mouse bone marrow colony growth in vitro. Aust J Exp Biol Med Sci. 1969 Aug;47(4):467–483. doi: 10.1038/icb.1969.51. [DOI] [PubMed] [Google Scholar]
  41. Stanley E. R., Metcalf D. The molecular weight of colony-stimulating factor (CSF). Proc Soc Exp Biol Med. 1971 Jul;137(3):1029–1031. doi: 10.3181/00379727-137-35721. [DOI] [PubMed] [Google Scholar]
  42. Stanners C. P., Eliceiri G. L., Green H. Two types of ribosome in mouse-hamster hybrid cells. Nat New Biol. 1971 Mar 10;230(10):52–54. doi: 10.1038/newbio230052a0. [DOI] [PubMed] [Google Scholar]
  43. TILL J. E., WHITMORE G. F., GULYAS S. Deoxyribonucleic acid synthesis in individual L-strain mouse cells. II. Effects of thymidine starvation. Biochim Biophys Acta. 1963 Jun 25;72:277–289. [PubMed] [Google Scholar]
  44. Virolainen M., Defendi V. Dependence of macrophage growth in vitro upon interaction with other cell types. Wistar Inst Symp Monogr. 1967;7:67–85. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES