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


CONCLUSIONS
The results point to PGM-Zn as a potent cytotoxicity-inducing agent, which also generates autoreactive NKT cells.
Mrakovcić-Sutić
Ines
I
Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Croatia.
Radosević-Stasić
Biserka
B
Simin
Marija
M
Muhvić
Damir
D
Rukavina
Daniel
D
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008099:Liver / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010457:Peptidoglycan; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015032:Zinc / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D010457:Peptidoglycan; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C032972:peptidoglycan pentapeptide-mDap3; D015032:Zinc