Apoptosis and chemokine induction after renal ischemia-reperfusion.

Authors :: Daemen MA
de Vries B
van't Veer C
Wolfs TG
Buurman WA
Source :: Transplantation [Transplantation] 2001 Apr 15; Vol. 71 (7), pp. 1007-11.
Publication Year :: 2001
Abstract: Background: One of the earliest prerequisites for the development of inflammation after ischemia-reperfusion (I/R) is local chemokine expression. We recently demonstrated that apoptosis, characterized by intracellular caspase-activation, contributes to the development of inflammation after I/R.<br />Methods: The contribution of apoptosis was investigated using the pan-caspase inhibitor Z-Val-Ala-Asp(OMe)-CH2F in a murine model of renal I/R. Renal expression of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC was studied using RT-PCR and immunohistology. Measuring myeloperoxidase activity and serum ureum and creatinine levels assessed neutrophil influx and kidney dysfunction.<br />Results: We demonstrate renal up-regulation of KC and MIP-2 after 1 to 16 hr of reperfusion. Treatment with the caspase inhibitor Z-Val-Ala-Asp(OMe)-CH2F effectively prevented I/R-induced renal apoptosis, KC, and MIP-2 up-regulation after 2 hr of reperfusion as well as neutrophil influx and functional impairment after 24 hr of reperfusion.<br />Conclusions: These data for the first time show that chemokine induction following I/R is dependent on caspase activation.