Carbon monoxide induces murine thymocyte apoptosis by a free radical-mediated mechanism.
Carbon monoxide (CO) induces acute or chronic toxicity, according to the level and duration of the exposure. Since chronic CO exposure was shown to have immunosuppressive effects (as it decreases the frequency of rat splenic immunocompetent cells and immunoglobulin production), we investigated the effect of CO on thymocytes, since these are the most sensitive cells to oxidative damage from the lymphoid lineage. We exposed thymocytes to CO, then determined their apoptotic index after 6 h of incubation at 37 degrees C using the fluorochrome Hoechst 33342 and electron microscopy and found an increase of apoptosis in CO-exposed thymocytes. Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), an antioxidant vitamin E analog, decreased CO-induced thymocyte apoptosis unlike methylene blue, L-nitroarginine methyl ester or pyrrolidine dithiocarbamate. We also observed that lipid peroxidation was increased in the CO-exposed thymocytes and that it was inhibited by Trolox. Our results suggest that CO induces thymocyte apoptosis by a free radical-mediated mechanism which can be inhibited by Trolox but which does not involve the activation of the guanylyl cyclase-cGMP pathway.
Turcanu
V
V
Université Louis Pasteur, Faculté de Pharmacie, Départment d'Immunologie, Strasbourg, France.
Dhouib
M
M
Gendrault
J L
JL
Poindron
P
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002248:Carbon Monoxide / Q000633:toxicity*; D004789:Enzyme Activation; D005260:Female; D005609:Free Radicals; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D005609:Free Radicals; D016328:NF-kappa B; D009569:Nitric Oxide; D002248:Carbon Monoxide; D006162:Guanylate Cyclase