Role of stimulated neutrophils from patients with systemic lupus erythematosus in tissue injury, with special reference to serum factors and increased active oxygen species generated by neutrophils.
To examine the possible correlation between tissue injury and neutrophil-produced active oxygen (AO) species in patients with systemic lupus erythematosus (SLE), we studied the capacity of the serum from six patients with untreated, active SLE to generate AO and release lysosomal enzymes by normal neutrophils. Cultured endothelial cells from human umbilical cord vein were incubated with serum-stimulated neutrophils to assess AO-induced tissue injury. Serum from patients with bacterial infections and healthy individuals served as controls. AO production was highest in the neutrophils stimulated with SLE patient-derived serum, while lysosomal enzyme release was only slightly increased. SLE neutrophils with or without stimulation and SLE serum-stimulated normal neutrophils produced significantly high levels of cytotoxicity upon coincubation with 51Cr-labeled human endothelial cells. These excessive cytotoxicities were reversed by the presence of superoxide dismutase and catalase, indicating the specificity of the AO effect on endothelial cell damage. These findings suggest that tissue damage in SLE may be partially due to excessive production of AO and that both neutrophils themselves and a serum factor which activates neutrophils are involved in the mechanism for vascular injury.
Niwa
Y
Y
Sakane
T
T
Shingu
M
M
Miyachi
Y
Y
D000293:Adolescent; D000328:Adult; D002470:Cell Survival; D004727:Endothelium / Q000473:pathology; D005260:Female; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D006878:Hydroxides / Q000633:toxicity; D008180:Lupus Erythematosus, Systemic / Q000473:pathology / Q000503:physiopathology*; D008247:Lysosomes / Q000201:enzymology; D009504:Neutrophils / Q000502:physiology*; D010100:Oxygen / Q000633:toxicity*; D013481:Superoxides / Q000633:toxicity
D005609:Free Radicals; D006878:Hydroxides; D013481:Superoxides; D006861:Hydrogen Peroxide; D010100:Oxygen