Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

PGM-zn as immunomodulator and antiproliferative agent

I Mrakovčić-Šutić MD, B Radošević-Stašić, P Md, J Ravlić-Gulan, P Md, M Šimin MD, M Ćuk, P Md, D Rukavina, P Md

Dept Physiology and Immunology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia,

AIM: In several models it was shown that peptidoglycan monomer (PGM), originally prepared by biosynthesis from culture fluids of penicillin-treated Brevibacterium divaricatum, has marked immunomodulating properties. However, even better immunostimulation in experimentally induced models of immunosuppression (halothane anesthesia, obstructive jaundice) or naturally occurring immunodeficient states (aging) we obtained with PGM-Zn, a new analogue of PGM, in which basic substance was linked with Zn. Recently, we observed that its stimulatory effects on humoral immunity might be both-T-cell dependent and independent, suggesting that PGM-Zn may enhance the co-stimulatory signals coming from the activated T cells, but may act also on mature B cells as polyclonal activator, without the T-cell help. METHODS: Owing to the observation that modulatory effects of PGM-Zn on humoral immunity markedly correlated with hepatic MHC class II upregulation, in this study we tested the involvement of T cells in these processes and analyzed the effects of hepatic mononuclear lymphatic cells, obtained from mice pretreated with PGM-Zn, on growth and phenotypic characteristics of malignant T-cell line Yac-1. RESULTS: The data have shown that in vivo depletion of CD4+ or CD4+ and CD8+ T lymphocytes significantly reduce hepatic class II expression, and that hepatic macrophages or NK cells activated in vivo with PGM-Zn, have greater cytotoxic properties, that similarly activated mononuclear cells from the spleen. CONCLUSIONS: The data emphasize that PGM-Zn, as a new molecule, which contains two constituents with known immunomodulating activities, has interesting, new, therapeutic properties and point to important cytotoxic effects of hepatic mononuclear cells in these events.

KEY WORDS: Peptidoglycan monomer linked with zinc, CD4 and/or CD8 depletion, hepatic macrophages and NK cells, cytotoxic test, growth of YAC-T cell line.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on synergistic therapies.