Tributyltin induces human neutrophil apoptosis and selective degradation of cytoskeletal proteins by caspases.

Tributyltin (TBT) has frequently been used as a pesticide and in biocidal paints for marine vessels, leading to its presence in the environment. Although TBT was recently found to induce apoptosis in different immune cells, by a mechanism that is not fully established, its effect on neutrophils is not known. In this study, it was found that TBT induced apoptosis in human neutrophils as assessed by cytology, flow cytometry, and degradation of the microfilament-associated protein gelsolin. Furthermore, data showed that TBT induced neutrophil apoptosis by a caspase-dependent mechanism, since addition of z-Val-Ala-Asp(MOe)-CH(2)F (z-VAD-FMK) in the culture prevented the effect of TBT. It was also found that the cytoskeletal proteins gelsolin, paxillin, and vimentin, but not vinculin, were degraded by TBT via caspases, as assessed by immunoblotting. Data indicate that gelsolin, paxillin, and vimentin are three caspase substrates involved in both spontaneous and TBT-induced neutrophil apoptosis. Cells were not necrotic as assessed by trypan blue dye exclusion, and this is in agreement with the absence of vinculin degradation. Evidence indicates that TBT-induced fragmentation of cytoskeletal proteins via caspases is a process that is tightly regulated.