Cd13 Is The Resistance Mechanism For Endothelial Interleukin-8 Inducing Apoptosis

We have reported that endothelial interleukin-8 (IL-8) induces apoptosis in leukemic cells in vitro and in vivo. and that the pentapeptide corresponding to the N-terminal region of endothelial IL-8 is essential for inducing apoptosis. However, some cell lines, such as NB4 were found to be resistant to the pro-apoptotic effect of endothelial IL-8. NB4 cells express a high level of CD13/aminopeptidase N, which is implicated in peptide degradation. Here, we investigated the relationship between cell-surface aminopeptidase activity and the apoptosis-inducing activity of endothelial IL-8. By the addition of aminopeptidase inhibitors, such as bestatin or mAb directed against CD13/aminopeptidase N, NB4 cells acquired sensitivity to the apoptosis-inducing activity of IL-8, Moreover, K562 cells transduced to express CD13, had the same levels of aminopeptidase activity as NB4, and were resistant to endothelial IL-8-induced apoptosis in vitro. Bestatin reversed endothelial IL-8-induced apoptosis in CD13-overexpressing K562 cells. Thus, in this study. we demonstrated that CD13 might play an important role in resistance to apoptosis in leukemic cells, and that the combination of endothelial IL-8 and bestatin is useful to CD13-expressing leukemic cells.