Immunoprotective properties of peptidoglycan monomer linked with zinc in cholestatic jaundice.
BACKGROUND
Previously it was shown that a new immunostimulator, peptidoglycan monomer linked with zinc (PGM-Zn), might have immunocorrective and hepatotropic effects. Owing to this in the present study we investigated its effects on jaundice-induced immunodysfunction, which might be responsible for serious peri- and postoperative complications in biliary obstruction.


METHODS
In vivo effects of PGM-Zn were analyzed in mice subjected to common bile duct ligation (CBDL), where we estimated phenotypic profile and cell cycle of thymocytes, splenocytes and phagocytic function of peritoneal macrophages. In vitro effects of PGM-Zn were evaluated on blastogenesis of human peripheral blood mononuclear cells (PBMNC), obtained from healthy donors and stimulated with anti-CD3 monoclonal antibody and/or PMA, in the presence or absence of jaundice serum obtained from patients with biliary calculosis.


CONCLUSIONS
Jaundice induced marked disarrangement of lymphatic homeostasis, which at several points might be blocked by PGM-Zn. In mice it delayed the CBDL-induced decline of CD4+ CD8+ thymocytes, decreased the proportion of CD8+ T cells, and increased the percentage of CD4- CD8- thymocytes, augmenting simultaneously the proportion of thymic cells in S and G2 + M phase of cycle. Similar hyperplastic reaction with increased percentage of CD4+, Ig+ and CD5+ cells was noticed in the spleen, together with the enhanced phagocytic ability of peritoneal macrophages. In human PBMNC jaundice reduced the percentages of CD3, CD5, CD4, CD8 and HLA-DR-expressing cells and increased the proportion of CD25 and perforin-positive lymphocytes. PGM-Zn given in vitro was able to abrogate the antiproliferative activity of jaundice serum on PMA and anti-CD3 + PMA-induced blastogenesis.
Ravlić-Gulan
J
J
Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Radosević-Stasić
B
B
Gulan
G
G
Stimac
D
D
Pavelić
K
K
Rukavina
D
D
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage* / Q000031:analogs & derivatives; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002779:Cholestasis / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010457:Peptidoglycan; D010587:Phagocytosis / Q000187:drug effects; D015032:Zinc / Q000008:administration & dosage*
D000276:Adjuvants, Immunologic; D010457:Peptidoglycan; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C032972:peptidoglycan pentapeptide-mDap3; D015032:Zinc