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

Ines Mrakovcic-Sutic, Biserka Radosevic-Stasic ； Marija Simin ； Damir Muhvic ； Daniel Rukavina

《Mediators of Inflammation》 2002卷 (2002/12) Pp. 129-135

https://doi.org/10.1080/09629350220131000

摘要

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 NK1.1^(high+), CD4^-CD8^-, CD69^+, and CD3^(intermediate)/NK1.1^+/IL2R-β^+ (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.

關鍵字

NK cells ； NK1.1 ； Intermediate T cell receptor expressing cells ； Cytotoxicity to YAC-1 and syngeneic thymocytes ； Liver and spleen ； Self-reacting NKT cells