Induction of apoptosis in human blood T cells by 7,8-dihydroneopterin: the difference between healthy controls and patients with systemic lupus erythematosus.
Neopterin (Neo) and 7,8-dihydroneopterin (H(2)Neo) are produced by human monocyte-derived macrophages upon stimulation with IFN-gamma. Increased amounts of Neo and H(2)Neo in human body fluids are found in many disorders, including viral infections and autoimmune diseases. Recent data suggest that neopterin derivatives may exhibit distinct biochemical functions activating redox-sensitive transcription factors and inducing apoptosis in various cell lines. In this study we investigated the effect of H(2)Neo on human peripheral blood T cells (PBT) from healthy blood donors in comparison with PBT isolated from patients with systemic lupus erythematosus (SLE). H(2)Neo induced apoptosis in healthy PBT in a concentration-dependent manner. In short time culture, a significantly lower ability of PBT isolated from patients with SLE to undergo apoptosis in response to H(2)Neo compared to healthy controls was detected. Our results suggest a possible role of the neopterin derivative H(2)Neo in T cell apoptosis mediated by stimulated monocytes/macrophages.
Wirleitner
Barbara
B
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Innsbruck, Austria.
Obermoser
Gerlinde
G
Böck
Günther
G
Neurauter
Gabriele
G
Schennach
Harald
H
Sepp
Norbert
N
Fuchs
Dietmar
D
D000328:Adult; D017304:Annexin A5; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000031:analogs & derivatives; D010835:Phytohemagglutinins / Q000494:pharmacology; D011621:Pteridines / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D017304:Annexin A5; D000975:Antioxidants; D016207:Cytokines; D010835:Phytohemagglutinins; D011621:Pteridines; D003208:Concanavalin A; C000976:7,8-dihydroneopterin; D019798:Neopterin