Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1983 Dec;42(3):1081–1085. doi: 10.1128/iai.42.3.1081-1085.1983

Modulation of myelopoiesis in vivo by synthetic adjuvant-active muramyl peptides: induction of colony-stimulating activity and stimulation of stem cell proliferation.

A Galelli, L Chedid
PMCID: PMC264410  PMID: 6605930

Abstract

Modulation of myelopoiesis by three synthetic muramyl peptides was investigated in vivo. Two adjuvant-active compounds (N-acetylmuramyl dipeptide [MDP] and MDP-butyl-ester) elicited significant responses in DBA/2 mice characterized by a rise in the level of monocyte-macrophage colony-stimulating activity in serum, a proliferation of multipotential stem cells in the bone marrow, and an expansion of granulocyte-macrophage progenitors in the spleen. In contrast, the adjuvant-inactive stereoisomer MDP(D-D) induced only low levels of circulating colony-stimulating activity. Thus, MDP or MDP-butyl-ester injection could induce a greater number of macrophages and therefore enhance both specific and nonspecific immunity.

Full text

PDF
1081

Selected References

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

  1. Adam A., Ciorbaru R., Ellouz F., Petit J. F., Lederer E. Adjuvant activity of monomeric bacterial cell wall peptidoglycans. Biochem Biophys Res Commun. 1974 Feb 4;56(3):561–567. doi: 10.1016/0006-291x(74)90640-8. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Chedid L. A., Parant M. A., Audibert F. M., Riveau G. J., Parant F. J., Lederer E., Choay J. P., Lefrancier P. L. Biological activity of a new synthetic muramyl peptide adjuvant devoid of pyrogenicity. Infect Immun. 1982 Feb;35(2):417–424. doi: 10.1128/iai.35.2.417-424.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chedid L., Audibert F., Lefrancier P., Choay J., Lederer E. Modulation of the immune response by a synthetic adjuvant and analogs. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2472–2475. doi: 10.1073/pnas.73.7.2472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chedid L., Parant M., Parant F., Lefrancher P., Choay J., Lederer E. Enhancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine) and several analogs. Proc Natl Acad Sci U S A. 1977 May;74(5):2089–2093. doi: 10.1073/pnas.74.5.2089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ellouz F., Adam A., Ciorbaru R., Lederer E. Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res Commun. 1974 Aug 19;59(4):1317–1325. doi: 10.1016/0006-291x(74)90458-6. [DOI] [PubMed] [Google Scholar]
  7. Leclerc C., Löwy I., Chedid L. Influence of MDP and of some analogous synthetic glycopeptides on the in vitro mouse spleen cell viability and immune response to sheep erythrocytes. Cell Immunol. 1978 Jul;38(2):286–293. doi: 10.1016/0008-8749(78)90059-x. [DOI] [PubMed] [Google Scholar]
  8. Lefrancier P., Choay J., Derrien M., Lederman I. Synthesis of N-acetyl-muramyl-L-alanyl-D-isoglutamine, an adjuvant of the immune response, and of some n-acetyl-muramyl-peptide analogs. Int J Pept Protein Res. 1977;9(4):249–257. doi: 10.1111/j.1399-3011.1977.tb03488.x. [DOI] [PubMed] [Google Scholar]
  9. Lefrancier P., Derrien M., Jamet X., Choay J., Lederer E., Audibert F., Parant M., Parant F., Chedid L. Apyrogenic, adjuvant-active N-acetylmuramyl-dipeptides. J Med Chem. 1982 Jan;25(1):87–90. doi: 10.1021/jm00343a018. [DOI] [PubMed] [Google Scholar]
  10. Merser C., Sinay P., Adam A. Total synthesis and adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res Commun. 1975 Oct 27;66(4):1316–1322. doi: 10.1016/0006-291x(75)90503-3. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Parant M., Parant F., Chedid L. Enhancement of the neonate's nonspecific immunity to Klebsiella infection by muramyl dipeptide, a synthetic immunoadjuvant. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3395–3399. doi: 10.1073/pnas.75.7.3395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Quesenberry P., Morley A., Stohlman F., Jr, Rickard K., Howard D., Smith M. Effect of endotoxin on granulopoiesis and colony-stimulating factor. N Engl J Med. 1972 Feb 3;286(5):227–232. doi: 10.1056/NEJM197202032860502. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Staber F. G., Gisler R. H., Schumann G., Tarcsay L., Schläfli E., Dukor P. Modulation of myelopoiesis by different bacterial cell-wall components: induction of colony-stimulating activity (by pure preparations, low-molecular-weight degradation products, and a synthetic low-molecular analog of bacterial cell-wall components) in vitro. Cell Immunol. 1978 Apr;37(1):174–187. doi: 10.1016/0008-8749(78)90185-5. [DOI] [PubMed] [Google Scholar]
  16. Stanley E. R., Cifone M., Heard P. M., Defendi V. Factors regulating macrophage production and growth: identity of colony-stimulating factor and macrophage growth factor. J Exp Med. 1976 Mar 1;143(3):631–647. doi: 10.1084/jem.143.3.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. TILL J. E., McCULLOCH E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961 Feb;14:213–222. [PubMed] [Google Scholar]
  18. Tanaka A., Nagao S., Nagao R., Kotani S., Shiba T., Kusumoto S. Stimulation of the reticuloendothelial system of mice by muramyl dipeptide. Infect Immun. 1979 May;24(2):302–307. doi: 10.1128/iai.24.2.302-307.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wachsmuth E. D., Wüst B. Effect of bestatin and muramyl-dipeptide on macrophage-bound aminopeptidase. Hoppe Seylers Z Physiol Chem. 1981 May;362(5):563–568. [PubMed] [Google Scholar]
  20. Waters R. V., Ferraresi R. W. Muramyl dipeptide stimulation of particle clearance in several animal species. J Reticuloendothel Soc. 1980 Nov;28(5):457–471. [PubMed] [Google Scholar]
  21. Wu M. C., Yunis A. A. Common pattern of two distinct types of colony-stimulating factor in human tissues and cultured cells. J Clin Invest. 1980 Mar;65(3):772–775. doi: 10.1172/JCI109726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wuest B., Wachsmuth E. D. Stimulatory effect of N-acetyl Muramyl dipeptide in vivo: proliferation of bone marrow progenitor cells in mice. Infect Immun. 1982 Aug;37(2):452–462. doi: 10.1128/iai.37.2.452-462.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES