Apoptosis of blood mononuclear cells in alcoholic liver cirrhosis. The influence of in vitro ethanol treatment and zinc supplementation.
Ethanol consumption induces apoptosis in a variety of tissues, among others in liver and lymphoid tissue. Zinc has been shown to influence apoptosis of blood mononuclear cells by inhibiting the mitochondrial pathway of cell death. The aim of this study was to examine the influence of zinc on spontaneous and in vitro alcohol-induced apoptosis of peripheral blood mononuclear cells (PBMCs) of patients with alcoholic cirrhosis. PBMCs were isolated from the blood of 26 patients with cirrhosis and 20 healthy controls. PBMCs and among them CD4+ T helper cells of cirrhotic patients exhibited accelerated spontaneous (without treatment) apoptosis in vitro. When apoptosis was induced in vitro by treating cells with 80 mM ethanol, CD8+ T lymphocytes of a healthy control were more sensitive to ethanol treatment than those of cirrhotic patients. Thirty micromolar zinc supplementation inhibited both spontaneous and ethanol-induced apoptosis of immune cells derived from the blood of the healthy control and cirrhotic patients. In sera of patients with cirrhosis, an elevated level of IL-12, but also sFas (CD95) and sFas ligand (sFasL) was detected. Moreover, in vitro, PBMCs of cirrhotic patients spontaneously released more sFas and sFasL than control PBMCs. Ethanol treatment significantly increased sFas, but decreased sFasL release from PBMCs of cirrhotic patients, while it only slightly affected control cells. As zinc supplementation did not significantly influence sFas or sFasL release, it seems likely that it is rather the mitochondrial pathway of ethanol-related immune cell death that may be inhibited by zinc supplementation.
Szuster-Ciesielska
Agnieszka
A
Department of Virology and Immunology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland. szustera@hektor.UMCS.LUBLIN.PL
Daniluk
Jadwiga
J
Bojarska-Junak
Agnieszka
A
D000328:Adult; D017209:Apoptosis; D016022:Case-Control Studies; D000431:Ethanol / Q000494:pharmacology*; D053222:Fas Ligand Protein; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*; D019014:fas Receptor
C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D018664:Interleukin-12; D000431:Ethanol; D005978:Glutathione; D015032:Zinc