Superoxide anion production and degranulation of rat neutrophils in response to acetaldehyde-altered liver cell membranes

Abstract

1. Rat liver membrane vesicles were exposed to acetaldehyde, with or without reduction of the resultant adducts formed. 2. Superoxide anion production and degranulation of rat neutrophils, upon stimulation with the liver membrane vesicles, were measured by cytochrome c reduction before and after the addition of superoxide dismutase, and β-glucuronidase release respectively. 3. Preincubation with acetaldehyde significantly enhanced superoxide anion production by both the reduced and non-reduced membrane samples (1.7-fold and 4.4-fold, respectively). 4. Preincubation with acetaldehyde significantly enhanced degranulation (1.5-fold) of neutrophils in response to the non-reduced membranes only. The reductive process itself caused a marked increase (2.4-fold) in the ability of the membrane vesicles to stimulate degranulation. 5. Cytochalasin B, an inhibitor of phagocytosis, did not reduce degranulation, implying that it occurred as a consequence of cell surface stimulation. 6. Neutrophil superoxide anion production and lysosomal enzyme release in response to acetaldehyde-altered liver cell membranes could be an important mechanism of hepatocyte injury in alcoholic liver disease.