| Research Abstract |
We purified three kinds of undiscovered factor that induces apoptosis in leukemic cells from HL-60 human myeloid leukemic cell-conditioned media. We identified the N-terminal amino acid sequences, and we demonstrated that one of our factors, endothelial interleukin-8 induced apoptosis in both leukemic and lymphoma cells. Monocyte-derived IL-8 did not induce apoptosis, and we demonstrated that N-terminal AVLPR peptide induced apoptosis. We demonstrated that both endothelial IL-8 and peptide AVLPR induced apoptosis and antitumor effect in leukemia-bearing mice in vivo. NB4, derived from acute promyelocytic leukemia, is a resistant cell line for endothelial IL-8-induced apoptosis. We observed that expression of CD13 antigen, that is an aminopeptidase N, is related to resistance for endothelial IL-8-induced apoptosis. Neutralizing antibody for CD13 inhibited aminopeptidase N activity, and aminopeptidase inhibitors reversed resistance for endothelial IL-8-induced apoptosis.
CD13 is one of the resistant mechanism for endothelial IL-8-induced apoptosis. Next, we demonstrated that b2-microglobulin induced apoptosis in leukemia and lymphoma cells. β2-microglobulin induced apoptosis via activation of caspase-3 and NF-kB pathway, Anti-HLA antibodies induced apoptosis in T cell leukemic cells that is different pathway from b2-microglobulin-induced pathway. We also demonstrated that complement factor Bb induced apoptosis via CD11c receptor in leukemia cells. We hope that our apoptosis-inducing factors will help purging tumor cells in peripheral blood collected samples in cancer patients.
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