Mrakovcić-Sutić Ines, Radosević-Stasić Biserka, Simin Marija, Muhvić Damir, Rukavina Daniel
Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Croatia.
Mediators Inflamm. 2002 Apr;11(2):129-35. doi: 10.1080/09629350220131000.
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.
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.
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.
The results point to PGM-Zn as a potent cytotoxicity-inducing agent, which also generates autoreactive NKT cells.
肽聚糖单体(PGM)最初是通过青霉素处理的分叉短杆菌培养液的生物合成制备的,是一种免疫刺激剂,在其基本分子中添加锌(Zn)可能会提高其活性。
为了测试这种新类似物可能的细胞毒性作用,我们分析了PGM-Zn和PGM改变肝和脾单核淋巴细胞表型谱以及影响恶性T细胞系YAC-1和同基因胸腺细胞生长的能力。
C57BL/6小鼠主要用PGM-Zn预处理6天(腹腔注射10mg/kg),显著提高了肝脏中NK1.1high+、CD4-CD8-、CD69+和CD3intermediate/NK1.1+/IL2R-β+(NKT)细胞的比例,以及脾脏中主要组织相容性复合体II类+、CD69+和CD8+细胞的比例。这两种细胞对YAC-1和同基因胸腺细胞均具有高度细胞毒性,添加肝细胞时YAC-1的破坏增加70%,添加脾细胞时增加30%。胸腺细胞的破坏分别增加了10%和50%。
结果表明PGM-Zn是一种有效的细胞毒性诱导剂,它还能产生自身反应性NKT细胞。