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Environ Toxicol Pharmacol. 2002 Jul;11(3-4):159-65.

The role of calpains in apoptotic changes in isolated hepatocytes after attack by Natural Killer cells.

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Division of Toxicology, Leiden-Amsterdam Center for Drug Research, Leiden University, Sylvius Laboratories, P.O. Box 9503, 2300 RA, Leiden, The Netherlands.


Previously, we showed that interleukin-2 activated Natural Killer cells (A-NK cells) in vitro rapidly induced apoptosis in freshly isolated rat hepatocytes (Blom et al., 1999. Hepatology 29 (3): 785-792) which was caused by a rapid decrease in the mitochondrial membrane potential and activation of caspases. In the present study we investigated the involvement of calpains in A-NK cell-induced apoptosis in isolated hepatocytes. When NK cells and hepatocytes were incubated in the presence of a calpain inhibitor the number of apoptotic cells decreased from 46 to 36%. However, more hepatocytes became necrotic (48 vs. 30%) as compared to the uninhibited situation. Inhibition of the calpains alone could not prevent the induction of the nuclear and cytoskeletal disruptions occurring in the hepatocytes. Inhibition of both calpains and caspases increased the number of necrotic cells as compared to incubation with a single inhibitor. However, the damage to the cytoskeleton of the surviving cells was completely inhibited. We conclude that calpains play a role in induction of apoptosis by NK cells. However, their role is limited as compared to caspases.

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