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. 1976 Nov;85(2):465–478.

Regulation of immunity and inflammation by mediators from macrophages.

E R Unanue, D I Beller, J Calderon, J M Kiely, M J Stadecker
PMCID: PMC2032565  PMID: 136901

Abstract

Mononuclear phagocytes secrete a number of materials into the extracellular environment. The materials secreted by phagocytes can be grouped into three categories: a) enzymes affecting extracellular proteins (collagenase, elastase, lysosomal proteases, plasminogen activators), b) materials involved in defense processes (complement proteins, interferons, lysozyme), and c) factors regulating activities of surrounding cells. The latter include lymphostimulatory molecules, a colony-stimulating factor, and inhibitors of cell growth. The conditions for secretion of the materials depend on the activity of the phagocytes. The lymphostimulatory molecules secreted by macrophages exert various effects: 1) an increase in DNA synthesis of lymphocytes, 2) a maturation of early thymocytes to mature T cells, and 3) the differentiation of some B cells to antibody-secreting cells. The mitogenic principle has been partially isolated as a protein of 15,000 to 20,000 daltons. The secretion of lymphostimulatory molecules is increased following uptake of various materials by macrophages or by addition of activated T cells to macrophage cultures.

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Selected References

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

  1. Acton J. D., Myrvik Q. N. Production of interferon by alveolar macrophages. J Bacteriol. 1966 Jun;91(6):2300–2304. doi: 10.1128/jb.91.6.2300-2304.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Atkins E., Bodel P., Francis L. Release of an endogenous pyrogen in vitro from rabbit mononuclear cells. J Exp Med. 1967 Aug 1;126(2):357–384. doi: 10.1084/jem.126.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bach F. H., Alter B. J., Solliday S., Zoschke D. C., Janis M. Lymphocyte reactivity in vitro. II. Soluble reconstituting factor permitting response of purified lymphocyte. Cell Immunol. 1970 Jul;1(2):219–227. doi: 10.1016/0008-8749(70)90009-2. [DOI] [PubMed] [Google Scholar]
  4. Bodel P., Atkins E. Release of endogenous pyrogen by human monocytes. N Engl J Med. 1967 May 4;276(18):1002–1008. doi: 10.1056/NEJM196705042761803. [DOI] [PubMed] [Google Scholar]
  5. Briggs R. S., Perillie P. E., Finch S. C. Lysozyme in bone marrow and peripheral blood cells. J Histochem Cytochem. 1966 Feb;14(2):167–170. doi: 10.1177/14.2.167. [DOI] [PubMed] [Google Scholar]
  6. Calderon J., Kiely J. M., Lefko J. L., Unanue E. R. The modulation of lymphocyte functions by molecules secreted by macrophages. I. Description and partial biochemical analysis. J Exp Med. 1975 Jul 1;142(1):151–164. doi: 10.1084/jem.142.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Calderon J., Williams R. T., Unanue E. R. An inhibitor of cell proliferation released by cultures of macrophages. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4273–4277. doi: 10.1073/pnas.71.11.4273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chervenick P. A., Boggs D. R. Bone marrow colonies: stimulation in vitro by supernatant from incubated human blood cells. Science. 1970 Aug 14;169(3946):691–692. doi: 10.1126/science.169.3946.691. [DOI] [PubMed] [Google Scholar]
  9. Davies P., Page R. C., Allison A. C. Changes in cellular enzyme levels and extracellular release of lysosomal acid hydrolases in macrophages exposed to group A streptococcal cell wall substance. J Exp Med. 1974 May 1;139(5):1262–1282. doi: 10.1084/jem.139.5.1262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Einstein L. P., Schneeberger E. E., Colten H. R. Synthesis of the second component of complement by long-term primary cultures of human monocytes. J Exp Med. 1976 Jan 1;143(1):114–126. doi: 10.1084/jem.143.1.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Gery I., Handschumacher R. E. Potentiation of the T lymphocyte response to mitogens. III. Properties of the mediator(s) from adherent cells. Cell Immunol. 1974 Mar 30;11(1-3):162–169. doi: 10.1016/0008-8749(74)90016-1. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Golde D. W., Finley T. N., Cline M. J. Production of colony-stimulating factor by human macrophages. Lancet. 1972 Dec 30;2(7792):1397–1399. doi: 10.1016/s0140-6736(72)92966-2. [DOI] [PubMed] [Google Scholar]
  16. Gordon S., Unkeless J. C., Cohn Z. A. Induction of macrophage plasminogen activator by endotoxin stimulation and phagocytosis: evidence for a two-stage process. J Exp Med. 1974 Oct 1;140(4):995–1010. doi: 10.1084/jem.140.4.995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hahn H. H., Char D. C., Postel W. B., Wood W. B., Jr Studies on the pathogenesis of fever. XV. The production of endogenous pyrogen by peritoneal macrophages. J Exp Med. 1967 Aug 1;126(2):385–394. doi: 10.1084/jem.126.2.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. KONO Y., HO M. THE ROLE OF THE RETICULOENDOTHELIAL SYSTEM IN INTERFERON FORMATION IN THE RABBIT. Virology. 1965 Jan;25:163–166. doi: 10.1016/0042-6822(65)90268-0. [DOI] [PubMed] [Google Scholar]
  20. Moore M. A., Spitzer G., Metcalf D., Penington D. G. Monocyte production of colony stimulating factor in familial cyclic neutropenia. Br J Haematol. 1974 May;27(1):47–55. doi: 10.1111/j.1365-2141.1974.tb06773.x. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Opitz H. G., Niethammer D., Lemke H., Flad H. D., Huget R. Inhibition of 3H-thymidine incorporation of lymphocytes by a soluble factor from macrophages. Cell Immunol. 1975 Apr;16(2):379–388. doi: 10.1016/0008-8749(75)90126-4. [DOI] [PubMed] [Google Scholar]
  23. Osserman E. F., Lawlor D. P. Serum and urinary lysozyme (muramidase) in monocytic and monomyelocytic leukemia. J Exp Med. 1966 Nov 1;124(5):921–952. doi: 10.1084/jem.124.5.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pantalone R. M., Page R. C. Lymphokine-induced production and release of lysosomal enzymes by macrophages. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2091–2094. doi: 10.1073/pnas.72.6.2091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stecher V. J., Thorbecke G. J. Sites of synthesis of serum proteins. OI. Serum proteins produced by macrophages in vitro. J Immunol. 1967 Oct;99(4):643–652. [PubMed] [Google Scholar]
  26. Ulrich F. A dialyzable protein synthesis inhibitor released by mammalian cells in vitro. Biochem Biophys Res Commun. 1974 Oct 23;60(4):1453–1459. doi: 10.1016/0006-291x(74)90361-1. [DOI] [PubMed] [Google Scholar]
  27. Unanue E. R., Kiely J. M., Calderon J. The modulation of lymphocyte functions by molecules secreted by macrophages. II. Conditions leading to increased secretion. J Exp Med. 1976 Jul 1;144(1):155–166. doi: 10.1084/jem.144.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wahl L. M., Wahl S. M., Mergenhagen S. E., Martin G. R. Collagenase production by endotoxin-activated macrophages. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3598–3601. doi: 10.1073/pnas.71.9.3598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Werb Z., Gordon S. Elastase secretion by stimulated macrophages. Characterization and regulation. J Exp Med. 1975 Aug 1;142(2):361–377. doi: 10.1084/jem.142.2.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Werb Z., Gordon S. Secretion of a specific collagenase by stimulated macrophages. J Exp Med. 1975 Aug 1;142(2):346–360. doi: 10.1084/jem.142.2.346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wood D. D., Gaul S. L. Enhancement of the humoral response of T cell-depleted murine spleens by a factor derived from human monocytes in vitro. J Immunol. 1974 Sep;113(3):925–933. [PubMed] [Google Scholar]

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