Abstract:
:The in vitro toxicity of the reactive oxygen species generating enzyme xanthine oxidoreductase (XOR) to human peripheral blood lymphocytes was studied after stimulation with phytohaemoagglutinin or anti-CD3/CD28 antibodies. Apoptosis and necrosis were induced by the XOR/hypoxanthine system in a time- and concentration-dependent manner. CD8+ lymphocytes showed a higher sensitivity than CD4+ cells to the XOR/hypoxanthine system. The occurrence of apoptosis was demonstrated by annexin-V binding to injured cell membrane, which was the most precocious alteration observed, followed by the increment of transglutaminase activity, which was significant at the lowest XOR concentration used. Nuclear damage was assessed by the increased hypodiploid nuclei and by DNA migration on gel electrophoresis, which turned to an apoptotic pattern before the occurrence of cell membrane necrotic lesions. Apoptosis was induced by XOR activity proportionally to substrate concentration and was prevented by the competitive enzyme inhibitor, allopurinol. The hydrogen peroxide scavenging enzyme, catalase, gave a higher protection than superoxide dismutase from the toxicity caused by the XOR/hypoxanthine system. Necrosis occurs in a variable percentage indicating that reactive oxygen species may trigger both apoptosis and necrosis in proliferating human lymphocytes, mostly depending on XOR concentration.
journal_name
Free Radic Resjournal_title
Free radical researchauthors
Battelli MG,Musiani S,Tazzari PL,Stirpe Fdoi
10.1080/10715760100301191keywords:
subject
Has Abstractpub_date
2001-12-01 00:00:00pages
665-79issue
6eissn
1071-5762issn
1029-2470journal_volume
35pub_type
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pub_type: 杂志文章,评审
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