CARBON-MONOXIDE INDUCES MURINE THYMOCYTE APOPTOSIS BY A FREE RADICAL-MEDIATED MECHANISM

Carbon monoxide (CO) induces acute or chronic toxicity, according to t he level and duration of the exposure. Since chronic CO exposure was s hown to have immunosuppressive effects (as it decreases the frequency of rat splenic immunocompetent cells and immunoglobulin production), w e investigated the effect of CO on thymocytes, since these are the mos t sensitive cells to oxidative damage from the lymphoid lineage. We ex posed thymocytes to CO, then determined their apoptotic index after 6 h of incubation at 37 degrees C using the fluorochrome Hoechst 33342 a nd electron microscopy and found an increase of apoptosis in CO-expose d thymocytes. Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxyli c acid), an antioxidant vitamin E analog, decreased CO-induced thymocy te apoptosis unlike methylene blue, L-nitroarginine methyl ester or py rrolidine dithiocarbamate. We also observed that lipid peroxidation wa s increased in the CO-exposed thymocytes and that it was inhibited by Trolox. Our results suggest that CO induces thymocyte apoptosis by a f ree radical-mediated mechanism which can be inhibited by Trolox but wh ich does not involve the activation of the guanylyl cyclase-cGMP pathw ay.