Augmentation of NKT and NK cell-mediated cytotoxicity by peptidoglycan monomer linked with zinc

Mediators Inflamm. 2002 Apr;11(2):129-35. doi: 10.1080/09629350220131000.

Abstract

Background: Peptidoglycan monomer (PGM), which was originally prepared by biosynthesis from culture fluids of penicillin-treated Brevibacterium divaricatum, is an immunostimulator, the activities of which might be improved by addition of zinc (Zn) to the basic molecule.

Methods: To test the possible cytotoxic effects of this new analogue, we analyzed the ability of PGM-Zn and PGM to change the phenotypic profile of hepatic and splenic mononuclear lymphatic cells and to affect the growth of malignant T-cell line YAC-1 and syngeneic thymocytes.

Results: Pretreatment of C57BL/6 mice primarily with PGM-Zn over 6 days (10/mg/kg intraperitoneally) significantly enhanced the proportions of NK1.1high+, CD4-CD8-, CD69+, and CD3intermediate/NK1.1+/IL2R-beta+ (NKT) cells in the liver, and major histocompatibility complex class II+, CD69+, and CD8+ cells in the spleen. Both types of cells were highly cytotoxic against YAC-1 and syngeneic thymocytes, increasing the destruction of YAC-1 by 70% on addition of hepatic cells and by 30% on addition of splenic cells. Destruction of thymocytes increased by 10 and 50%, respectively.

Conclusion: The results point to PGM-Zn as a potent cytotoxicity-inducing agent, which also generates autoreactive NKT cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives*
  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology*
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Cytotoxicity, Immunologic / drug effects*
  • Immunophenotyping
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Liver / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptidoglycan
  • Spleen / cytology
  • Spleen / immunology
  • Zinc / pharmacology*

Substances

  • Adjuvants, Immunologic
  • Peptidoglycan
  • Acetylmuramyl-Alanyl-Isoglutamine
  • peptidoglycan pentapeptide-mDap3
  • Zinc