Hydroxyl radical scavengers inhibit TNF-alpha production in mononuclear cells but not in polymorphonuclear leukocytes.
The hydroxyl radical (HO*) scavengers dimethylthiourea (DMTU), tetramethylthiourea (TMTU), dimethylsulfoxide (DMSO) and deferoxamine (DFX), the latter being an iron chelator which prevents HO* formation by blocking the Fenton reaction, were found to inhibit TNF-alpha production in LPS-stimulated human PBMC but not in PMN. Furthermore, this effect was not LPS-specific, as TNF-alpha production was reduced by HO* radical scavengers to a similar extent upon stimulation of PBMC with immune complexes (IC), concanavalin A (Con A) and phorbol myristate acetate (PMA). Other scavengers such as glutathione (GSH), N-acetylcysteine (NAC), ascorbic acid (ASC) and mannitol (MAN) do not have effect on the production of TNF-alpha either in PBMC or PMN. These results provide evidence that the participation of ROI in the regulation of TNF-alpha production differ in different cell types. Particularly, the data presented in this work indicate that HO* radicals have a central role in the production of this inflammatory cytokine by human PBMC.
Vulcano
M
M
División Immunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina. postmaster@anmra.sld.ar
Rosa
M F
MF
Breyer
I
I
Isturiz
M A
MA
D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D017665:Hydroxyl Radical / Q000494:pharmacology*; D007739:L Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019255:NADPH Oxidases / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000975:Antioxidants; D016166:Free Radical Scavengers; D014409:Tumor Necrosis Factor-alpha; D017665:Hydroxyl Radical; D019255:NADPH Oxidases