Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1979 Aug 1;150(2):359–370. doi: 10.1084/jem.150.2.359

Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A- stimulated lymphocytes

PMCID: PMC2185631  PMID: 458379

Abstract

Activation of mouse peritoneal exudate macrophages, as evidenced by destruction of the intracellular protozoan parasite Leishmania enriettii, was obtained by incubation with supernates from concanavalin A (Con A)-stimulated syngeneic spleen cells. Parasites were not destroyed in macrophages exposed to control media. Supernate-induced activation was independent of the presence of Con A. The activating principle (macrophage activating factor, or MAF) was produced by Con A- stimulated lymphocytes in presence or absence of serum. In absence of serum, MAF synthesis was highest at Con A concentrations far below those required in serum-containing media. MAF production was reduced at Con A concentrations of 10 microgram/ml or above, probably a result of toxicity of the lectin for lymphocytes. MAF was detectable after 24 h of lymphocyte stimulation and increased up to 72 h; production appeared to be independent of DNA synthesis. Serum-free MAF was inactive when tested as such on macrophages. Full activity could be restored by addition of nanogram amounts of endotoxin or of FCS before assay. Endotoxin also considerably potentiated MAF activity in serum- containing supernates. Full intracellular parasite destruction was observed after contact of macrophages with MAF for 20 h. The continuous presence of MAF was not necessary for activation; a 10-h pulse was sufficient to induce macrophages to destroy all intracellular microorganisms within the next 38 h.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. Borges J. S., Johnson W. D., Jr Inhibition of multiplication of Toxoplasma gondii by human monocytes exposed to T-lymphocyte products. J Exp Med. 1975 Feb 1;141(2):483–496. doi: 10.1084/jem.141.2.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. COHN Z. A., BENSON B. THE IN VITRO DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES. II. THE INFLUENCE OF SERUM ON GRANULE FORMATION, HYDROLASE PRODUCTION, AND PINOCYTOSIS. J Exp Med. 1965 May 1;121:835–848. doi: 10.1084/jem.121.5.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen D. M., Di Sabato G. Effect of serum and serum components on the mitogen-induced proliferation of murine lymphocytes. Immunol Commun. 1977;6(4):395–410. doi: 10.3109/08820137709051976. [DOI] [PubMed] [Google Scholar]
  4. Christie G. H., Bomford R. Mechanisms of macrophage activation by Corynebacterium parvum. I. In vitro experiments. Cell Immunol. 1975 May;17(1):141–149. doi: 10.1016/s0008-8749(75)80014-1. [DOI] [PubMed] [Google Scholar]
  5. Clausen J. E. Migration inhibitory effect of cell-free supernatants from mixed human lymphocyte cultures. J Immunol. 1972 Feb;108(2):453–459. [PubMed] [Google Scholar]
  6. Cohn Z. A., Parks E. The regulation of pinocytosis in mouse macrophages. II. Factors inducing vesicle formation. J Exp Med. 1967 Feb 1;125(2):213–232. doi: 10.1084/jem.125.2.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fowles R. E., Fajardo I. M., Leibowitch J. L., David J. R. The enhancement of macrophage bacteriostasis by products of activated lymphocytes. J Exp Med. 1973 Oct 1;138(4):952–964. doi: 10.1084/jem.138.4.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Godal T., Rees R. J., Lamvik J. O. Lymphocyte-mediated modification of blood-derived macrophage function in vitro; inhibition of growth of intracellular mycobacteria with lymphokines. Clin Exp Immunol. 1971 Apr;8(4):625–637. [PMC free article] [PubMed] [Google Scholar]
  9. Gunther G. R., Wang J. L., Yahara I., Cunningham B. A., Edelman G. M. Concanavalin A derivatives with altered biological activities. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1012–1016. doi: 10.1073/pnas.70.4.1012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hibbs J. B., Jr, Taintor R. R., Chapman H. A., Jr, Weinberg J. B. Macrophage tumor killing: influence of the local environment. Science. 1977 Jul 15;197(4300):279–282. doi: 10.1126/science.327547. [DOI] [PubMed] [Google Scholar]
  11. Kasakura S. A blastogenic factor in unidirectional mixed cultures with x-irradiated cells. Transplantation. 1971 Feb;11(2):117–121. doi: 10.1097/00007890-197102000-00002. [DOI] [PubMed] [Google Scholar]
  12. Mauel J., Behin R., Biroum-Noerjasin, Rowe D. S. Mechanisms of protective immunity in experimental cutaneous leishmaniasis of the guinea-pig. I. Lack of effects of immune lymphocytes and of activated macrophages. Clin Exp Immunol. 1975 May;20(2):339–350. [PMC free article] [PubMed] [Google Scholar]
  13. Mauel J., Buchmüller Y., Behin R. Studies on the mechanisms of macrophage activation. I. Destruction of intracellular Leishmania enriettii in macrophages activated by cocultivation with stimulated lymphocytes. J Exp Med. 1978 Aug 1;148(2):393–407. doi: 10.1084/jem.148.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mooney J. J., Waksman B. H. Activation of normal rabbit macrophage monolayers by supernatants of antigen-stimulated lymphocytes. J Immunol. 1970 Nov;105(5):1138–1145. [PubMed] [Google Scholar]
  15. Nogueira N., Cohn Z. A. Trypanosoma cruzi: in vitro induction of macrophage microbicidal activity. J Exp Med. 1978 Jul 1;148(1):288–300. doi: 10.1084/jem.148.1.288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Novogrodsky A., Katchalski E. Lymphocyte transformation induced by concanavalin A and its reversion by methyl-alpha-D-mannopyranoside. Biochim Biophys Acta. 1971 Jan 28;228(2):579–583. doi: 10.1016/0005-2787(71)90064-5. [DOI] [PubMed] [Google Scholar]
  17. Pick E., Krejcí J., Turk J. L. Release of skin reactive factor from guinea-pig lymphocytes by mitogens. Nature. 1970 Jan 17;225(5229):236–238. doi: 10.1038/225236a0. [DOI] [PubMed] [Google Scholar]
  18. Piessens W. F., Remold H. G., David J. R. Increased responsiveness to macrophage-activating factor (MAF) after alteration of macrophage membranes. J Immunol. 1977 Jun;118(6):2078–2082. [PubMed] [Google Scholar]
  19. Remold H. G., David R. A., David J. R. Characterization of migration inhibitory factor (MIF) from guinea pig lymphocytes stimulated with concanavalin A. J Immunol. 1972 Sep;109(3):578–586. [PubMed] [Google Scholar]
  20. Russell S. W., Doe W. F., McIntosh A. T. Functional characterization of a stable, noncytolytic stage of macrophage activation in tumors. J Exp Med. 1977 Dec 1;146(6):1511–1520. doi: 10.1084/jem.146.6.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES