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. 1992 Nov;60(11):4891–4897. doi: 10.1128/iai.60.11.4891-4897.1992

Roles of peripheral leukocytes and tissue macrophages in antibacterial resistance induced by free or liposome-encapsulated muramyl tripeptide phosphatidylethanolamide.

P M Melissen 1, W van Vianen 1, I A Bakker-Woudenberg 1
PMCID: PMC258245  PMID: 1399000

Abstract

Administration of free muramyl tripeptide phosphatidylethanolamide (MTPPE) or liposome-encapsulated MTPPE (LE-MTPPE) in a twofold-lower dose at 24 h before bacterial inoculation resulted in clearance of intravenously inoculated Klebsiella pneumoniae by tissue macrophages, whereas in control mice, bacteria were not effectively cleared from the blood. In addition, MTPPE and LE-MTPPE led to increased numbers of leukocytes in the blood, which could compensate for the leukopenia in mice resulting from infection with K. pneumoniae. In an attempt to elucidate the relative contributions of the activation of tissue macrophages and the recruitment of leukocytes to the antibacterial resistance induced by MTPPE and LE-MTPPE, mice were infected intraperitoneally with K. pneumoniae. In these MTPPE- and LE-MTPPE treated mice, intraperitoneal influx of leukocytes and the phagocytic capacity of leukocytes were not higher than in untreated control mice. However, MTPPE- and LE-MTPPE-treated mice survived much longer; eventually 33% of the LE-MTPPE-treated mice survived, whereas all untreated control mice died as a result of bacterial septicemia. This prevention of early death appeared to be the result of an increased clearance of bacteria from the blood by activated tissue macrophages. It was observed that depletion of these tissue macrophages in liver and spleen abrogates the effect of LE-MTPPE treatment, indicating that tissue macrophages are of major importance in the LE-MTPPE-induced resistance against K. pneumoniae infection.

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Selected References

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  1. Ausobsky J. R., Scuitto M., Trachtenberg L. S., Polk H. C., Jr The role of muramyl dipeptide in the therapy of established experimental bacterial infection. Br J Exp Pathol. 1984 Feb;65(1):1–9. [PMC free article] [PubMed] [Google Scholar]
  2. Broudy V. C., Kaushansky K., Shoemaker S. G., Aggarwal B. B., Adamson J. W. Muramyl dipeptide induces production of hemopoietic growth factors in vivo by a mechanism independent of tumor necrosis factor. J Immunol. 1990 May 15;144(10):3789–3794. [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. Daemen T., Veninga A., Roerdink F. H., Scherphof G. L. In vitro activation of rat liver macrophages to tumoricidal activity by free or liposome-encapsulated muramyl dipeptide. Cancer Res. 1986 Sep;46(9):4330–4335. [PubMed] [Google Scholar]
  5. Dietrich F. M., Hochkeppel H. K., Lukas B. Enhancement of host resistance against virus infections by MTP-PE, a synthetic lipophilic muramyl peptide--I. Increased survival in mice and guinea pigs after single drug administration prior to infection, and the effect of MTP-PE on interferon levels in sera and lungs. Int J Immunopharmacol. 1986;8(8):931–942. doi: 10.1016/0192-0561(86)90095-0. [DOI] [PubMed] [Google Scholar]
  6. Drews J. The experimental and clinical use of immune-modulating drugs in the prophylaxis and treatment of infections. Infection. 1984 Mar-Apr;12(2):157–166. doi: 10.1007/BF01641705. [DOI] [PubMed] [Google Scholar]
  7. Galland R. B., Polk H. C. Non-specific stimulation of host defenses against a bacterial challenge in malnourished hosts. Br J Surg. 1982 Nov;69(11):665–668. doi: 10.1002/bjs.1800691112. [DOI] [PubMed] [Google Scholar]
  8. Gangemi J. D., Nachtigal M., Barnhart D., Krech L., Jani P. Therapeutic efficacy of liposome-encapsulated ribavirin and muramyl tripeptide in experimental infection with influenza or herpes simplex virus. J Infect Dis. 1987 Mar;155(3):510–517. doi: 10.1093/infdis/155.3.510. [DOI] [PubMed] [Google Scholar]
  9. Imai K., Tanaka A. Effect of muramyldipeptide, a synthetic bacterial adjuvant, on enzyme release from cultured mouse macrophages. Microbiol Immunol. 1981;25(1):51–62. doi: 10.1111/j.1348-0421.1981.tb00006.x. [DOI] [PubMed] [Google Scholar]
  10. Izbicki J. R., Raedler C., Anke A., Brunner P., Siebeck M., Leinisch E., Lüttiken R., Ruckdeschel G., Wilker D. K., Schweiberer L. Beneficial effect of liposome-encapsulated muramyl tripeptide in experimental septicemia in a porcine model. Infect Immun. 1991 Jan;59(1):126–130. doi: 10.1128/iai.59.1.126-130.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Koff W. C., Showalter S. D., Hampar B., Fidler I. J. Protection of mice against fatal herpes simplex type 2 infection by liposomes containing muramyl tripeptide. Science. 1985 Apr 26;228(4698):495–497. doi: 10.1126/science.2984772. [DOI] [PubMed] [Google Scholar]
  12. Lamont P. M., Maier K. G., Melton L., Polk H. C., Jr Stimulatory effects of muramyl dipeptide upon neutrophils isolated from a local bacterial infection. Br J Exp Pathol. 1987 Oct;68(5):655–661. [PMC free article] [PubMed] [Google Scholar]
  13. Masihi K. N., Kröger H., Lange W., Chedid L. Muramyl peptides confer hepatoprotection against murine viral hepatitis. Int J Immunopharmacol. 1989;11(8):879–886. doi: 10.1016/0192-0561(89)90109-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Masihi K. N., Lange W., Rohde-Schulz B., Chedid L. Muramyl dipeptide inhibits replication of human immunodeficiency virus in vitro. AIDS Res Hum Retroviruses. 1990 Mar;6(3):393–399. doi: 10.1089/aid.1990.6.393. [DOI] [PubMed] [Google Scholar]
  15. Mehta K., Juliano R. L., Lopez-Berestein G. Stimulation of macrophage protease secretion via liposomal delivery of muramyl dipeptide derivatives to intracellular sites. Immunology. 1984 Mar;51(3):517–527. [PMC free article] [PubMed] [Google Scholar]
  16. Melissen P. M., van Vianen W., Rijsbergen Y., Bakker-Woudenberg I. A. Free versus liposome-encapsulated muramyl tripeptide phosphatidylethanolamide in treatment of experimental Klebsiella pneumoniae infection. Infect Immun. 1992 Jan;60(1):95–101. doi: 10.1128/iai.60.1.95-101.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. O'Grady F. Strategies for potentiating chemotherapy in severe sepsis: some experimental pointers. J Antimicrob Chemother. 1984 Jun;13(6):535–546. doi: 10.1093/jac/13.6.535. [DOI] [PubMed] [Google Scholar]
  18. Ozaki T., Maeda M., Hayashi H., Nakamura Y., Moriguchi H., Kamei T., Yasuoka S., Ogura T. Role of alveolar macrophages in the neutrophil-dependent defense system against Pseudomonas aeruginosa infection in the lower respiratory tract. Amplifying effect of muramyl dipeptide analog. Am Rev Respir Dis. 1989 Dec;140(6):1595–1601. doi: 10.1164/ajrccm/140.6.1595. [DOI] [PubMed] [Google Scholar]
  19. Parant M. A., Audibert F. M., Chedid L. A., Level M. R., Lefrancier P. L., Choay J. P., Lederer E. Immunostimulant activities of a lipophilic muramyl dipeptide derivative and of desmuramyl peptidolipid analogs. Infect Immun. 1980 Mar;27(3):826–831. doi: 10.1128/iai.27.3.826-831.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Phillips N. C., Rioux J., Tsao M. S. Activation of murine Kupffer cell tumoricidal activity by liposomes containing lipophilic muramyl dipeptide. Hepatology. 1988 Sep-Oct;8(5):1046–1050. doi: 10.1002/hep.1840080511. [DOI] [PubMed] [Google Scholar]
  21. Phillips N. C., Tsao M. S. Inhibition of experimental liver tumor growth in mice by liposomes containing a lipophilic muramyl dipeptide derivative. Cancer Res. 1989 Feb 15;49(4):936–939. [PubMed] [Google Scholar]
  22. Polk H. C., Jr, Galland R. B., Ausobsky J. R. Nonspecific enhancement of resistance to bacterial infection: evidence of an effect supplemental to antibiotics. Ann Surg. 1982 Oct;196(4):436–441. doi: 10.1097/00000658-198210000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Polk H. C., Jr, Lamont P. M., Galland R. B. Containment as a mechanism of nonspecific enhancement of defenses against bacterial infection. Infect Immun. 1990 Jun;58(6):1807–1811. doi: 10.1128/iai.58.6.1807-1811.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Reisser D., Jeannin J. F., Lagadec P., Martin F. Comparative effect of muramyl dipeptide in vivo and in vitro on the tumoricidal activity of rat peritoneal macrophages. J Biol Response Mod. 1985 Oct;4(5):460–463. [PubMed] [Google Scholar]
  25. Van Rooijen N., Kors N., vd Ende M., Dijkstra C. D. Depletion and repopulation of macrophages in spleen and liver of rat after intravenous treatment with liposome-encapsulated dichloromethylene diphosphonate. Cell Tissue Res. 1990 May;260(2):215–222. doi: 10.1007/BF00318625. [DOI] [PubMed] [Google Scholar]
  26. Van Rooijen N. The liposome-mediated macrophage 'suicide' technique. J Immunol Methods. 1989 Nov 13;124(1):1–6. doi: 10.1016/0022-1759(89)90178-6. [DOI] [PubMed] [Google Scholar]
  27. Wachsmuth E. D. Stimulation of cell proliferation in rabbits by MTP-PE, a lipophilic muramyl peptide. Virchows Arch B Cell Pathol Incl Mol Pathol. 1988;54(4):195–206. doi: 10.1007/BF02899212. [DOI] [PubMed] [Google Scholar]
  28. Yamaguchi F., Akasaki M., Tsukada W. Induction of colony-stimulating factor and stimulation of stem cell proliferation by injection of muroctasin. Arzneimittelforschung. 1988 Jul;38(7A):980–983. [PubMed] [Google Scholar]
  29. van Rooijen N., Kors N., Kraal G. Macrophage subset repopulation in the spleen: differential kinetics after liposome-mediated elimination. J Leukoc Biol. 1989 Feb;45(2):97–104. doi: 10.1002/jlb.45.2.97. [DOI] [PubMed] [Google Scholar]

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