ACTIVATED ENDOTHELIAL-CELLS INDUCE APOPTOSIS IN LEUKEMIC-CELLS BY ENDOTHELIAL INTERLEUKIN-8

Tumor cells are eradicated by several systems, including Fas ligand-fa s and tumor necrosis factor (TNF)-tumor necrosis factor receptor (TNFR ). in the previous study, we purified an apoptosis-inducing factor (Al F) to homogeneity from a medium conditioned by PDBu-treated HL-60 cell s, N-terminal sequence analysis showed that AIF is identical to endoth elial interleukin-8 (IL-8). A navel apoptosis system, in which endothe lial cells participate via endothelial IL-8 release, is identified her e. Human umbilical vein cells (VE cells) produce and secrete IL-8 by s timulation of IL-1 alpha and TNF-alpha. Endothelial IL-8, which is sec reted from VE cells by stimulation of IL-1 alpha and TNF-alpha. induce s apoptosis in myelogenous leukemia cell line K562 cells. Monocyte-der ived IL-8 could not induce apoptosis in K562 cells. Moreover, interact ion between VE cells and K562 cells induces the release of endothelial IL-8 from VE cells, and the attached K562 cells undergo apoptosis. Mo reover, interactions between VE cell and other cell lines, such as HL- 60, U937, Jurkat, and Daudi, induce the secretion of endothelial IL-8 and the induction of apoptosis in cell lines. Endothelial IL-8 signifi cantly inhibits tumor growth of intraperitoneal and subcutaneous tumor mass of K562 cells and induces apoptosis in their cells in vivo. Endo thelial IL-8 plays an important role in apoptosis involving endothelia l cells, which may provide us with a new therapy for hematological mal ignancies. (C) 1998 by The American Society of Hematology.