Abnormalities of neutrophil phagocytosis, intracellular killing and metabolic activity in alcoholic cirrhosis and hepatitis.
Neutrophil functions of phagocytosis and intracellular killing of bacteria were examined in 40 patients with alcoholic cirrhosis of whom 18 had a superimposed acute alcoholic hepatitis. In 65% of these, defective neutrophil phagocytosis was demonstrable, and in 62.5% there was a defect of intracellular killing of either Staphylococcus aureus or Escherichia coli. Studies of the patients' serum failed to reveal inhibitors of neutrophil function. Additional assays of superoxide (O2-) and hydrogen peroxide production, hexose monophosphate shunt activity, degranulation and cellular levels of granule enzymes and glutathione revealed that these neutrophil defects are caused by both reduced production of superoxide and defects of degranulation. The hydrogen peroxide/superoxide molar ratio was raised in patients' neutrophils, and the strong inverse correlation found between the value of this ratio and intracellular levels of reduced glutathione would be consistent with the hypothesis that the neutrophils from patients with cirrhosis are unable to detoxify hydrogen peroxide effectively and that this is a result of reduced levels of glutathione in the cells. The consequent increase in oxidant stress, both intra- and extracellularly, may be the cause of phagocytic and degranulation defects. The reduced responses of patients' neutrophils may be caused by previous exposure of the cells to activating stimuli in circulation, as evidenced by depleted intracellular levels of granule enzymes and glutathione. Neutrophils from the patients with a superimposed acute alcoholic hepatitis had depressed phagocytosis in the early stages of incubation but, on the whole, neutrophils from these patients had a greater capacity for ingestion and killing of bacteria than neutrophils from patients with cirrhosis alone.(ABSTRACT TRUNCATED AT 250 WORDS)
D001770:Blood Bactericidal Activity; D003594:Cytoplasmic Granules / Q000201:enzymology; D004926:Escherichia coli / Q000276:immunology; D005978:Glutathione / Q000097:blood; D006519:Hepatitis, Alcoholic / Q000097:blood / Q000276:immunology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010427:Pentose Phosphate Pathway; D010587:Phagocytosis; D013211:Staphylococcus aureus / Q000276:immunology; D013481:Superoxides / Q000097:blood
D013481:Superoxides; D006861:Hydrogen Peroxide; D005978:Glutathione