Immunoregulating Effects of Peptidoglycan Monomer Linked with Zinc in Adult Mice

Abstract

Since it is well known that both zinc ions and bacterial immunostimulants influence the function of the immune system, in the present study we investigated the immunomodulating activity of a new analog of peptidoglycan monomer (PGM), in which the basic molecule was linked to zinc (PGM-Zn). Its effects in BALB/c mice, aged 10–12 months, were compared with the effects of equimolar doses of PGM and ZnCl₂. The treatment lasted 26 days (one i.p. injection every fifth day). The results showed that PGM-Zn may markedly enhance antibody production to sheep red blood cells, as well as spontaneous and concanavalin A (ConA-induced blastogenesis. The generation of plaque-forming cells in individual mouse was positively correlated with the expression of class II antigens in the liver and negatively correlated with the total quantity of hepatic proteins. PGM-Zn also induced the appearance of peritoneal macrophages, which in cocultures with syngeneic splenocytes were less able to enhance the spontaneous, and particularly the ConA-induced blastic transformation. The enhancing activities of PGM-Zn were in some respects more closely correlated with the action of PGM, whereas the induction of suppressive macrophages resembled more the activity of ZnCl₂. The data emphasize that PGM-Zn may both stimulate and inhibit immunoregulative pathways by mechanisms which are not identical to those of PGM or ZnCl₂.

Immunoprotective Properties of Peptidoglycan Monomer Linked with Zinc in Cholestatic Jaundice

“…3, 4), confirming that PGM-Zn may stimulate the proliferation of T lymphocytes and enhance the antibody production, acting as a polyclonal activator of B cells, or as a T cell-independent antigen type 2 [9]. In agreement with our previous findings [7, 8]it also markedly enhanced the expression of MHC class II antigens on hepatic mononuclear lymphatic cells (not shown) and corrected the diminished phagocytic ability of peritoneal macrophages (fig. 5).…”

“…PGM-Zn as a new metal complex of PGM was synthesized in an attempt to combine the immunostimulating properties of PGM [5, 6, 7, 8, 9]and Zn [15, 16]. Its enhancing effects on B cells seems to be related with its ability to potentiate the costimulatory signals coming from activated T cells and enhance the hepatic MHC class II expression [7].…”

“…Its enhancing effects on B cells seems to be related with its ability to potentiate the costimulatory signals coming from activated T cells and enhance the hepatic MHC class II expression [7]. Its effects on isotype switching to IgG1 and IgG2a correlated also with the changes in splenic CD4+, CD8+ and CD5+ cells, pointing to the regulatory role of these cells and/or their cytokines in PGM-Zn-induced immunostimulation [9].…”

“…Surface phenotype of human PBL and murine thymocytes and splenocytes was identified by direct immunofluorescence analysis on FACScan (Becton Dickinson, Immunocytometry Systems, Mountain View, Calif.), using FACScan Research Software, as previously described [7]. Briefly, after rewashing the previously made suspension of cells in RPMI 1640, the cell number was adjusted to 1 × 10 6 /ml.…”

“…Its immunostimulating and antimetastatic activity were emphasized in many experimental protocols [5, 6]. Recently, however, we reported that PGM linked with Zn (PGM-Zn) had an even better immunocorrective potential than PGM, which possessed a greater enhancing activity on MHC class II expression in the liver and was able to induce the generation of peritoneal exudate cells (PEC) with suppressive activity on blastic proliferation of syngeneic splenocytes [7, 8]. Furthermore, using the model of in vivo T subset cell depletion, we found that stimulating activity of PGM-Zn on humoral immunity might include both polyclonal stimulation of B lymphocytes and generation of costimulatory signals from T cells, implying that it had some characteristic of T-independent-2 antigens [9].…”