Mechanism on the Cell Death of T-lymphocytes Induced by Organotin in Vitro

Abstract

Organotin compounds are toxic to the immune system. Alkyltin compounds such as dibutyltin (DBT) and tributyltin (TBT) cause severe thymus atrophy. At histopathological examination, there is marked depletion of lymphocytes and the depletion is due to the cell death. In this study, the mechanism on the cell death induced by DBT or TBT was investigated from the angle of apoptosis in T-lymphocytes.

The results revealed that DBT induced caspase-independent cell death (necrosis), whereas TBT induced caspase dependent cell death (apoptosis). Furthermore, we demonstrated the mechanism on TBT-induced apoptosis. Bid cleavage by activation of caspase-8 produced tBid and released cytochrome c from mitochondria. Release of cytochrome c induced the activation of caspase-3 through caspase-9. CAD activated by caspase-3 induced DNA fragmentation. That is to say, it was elucidated that TBT induced caspase-dependent and mitochondria-mediated cell death.