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Blood, Vol. 92 No. 8 (October 15), 1998:
pp. 2672-2680
RAPID COMMUNICATION
Activated Endothelial Cells Induce Apoptosis in Leukemic Cells by
Endothelial Interleukin-8
Yasuhito Terui,
Masayuki Ikeda,
Hiroshi Tomizuka,
Tadashi Kasahara,
Tetsuya Ohtsuki,
Masaya Uwai,
Masaki Mori,
Takehito Itoh,
Miyuki Tanaka,
Muneo Yamada,
Seiichi Shimamura,
Yukihito Ishizaka,
Kazuma Ikeda,
Keiya Ozawa,
Yasusada Miura, and
Kiyohiko Hatake
From the Division of Hematology, Department of Internal Medicine,
Jichi Medical School, Kawachi-gun, Tochigi, Japan; the Biochemical
Research Laboratory, Morinaga Milk Industry Co Ltd, Zama City,
Kanagawa, Japan; and the Department of Biochemistry, Kyoritsu College
of Pharmåcy, Minato-ku, Tokyo, Japan.
Tumor cells are eradicated by several systems, including Fas
ligand-Fas and tumor necrosis factor (TNF)-tumor necrosis factor receptor (TNFR). In the previous study, we purified an
apoptosis-inducing factor (AIF) to homogeneity from a medium
conditioned by PDBu-treated HL-60 cells. N-terminal sequence analysis
showed that AIF is identical to endothelial interleukin-8 (IL-8). A
novel apoptosis system, in which endothelial cells participate via
endothelial IL-8 release, is identified here. Human umbilical vein
cells (VE cells) produce and secrete IL-8 by stimulation of IL-1 and
TNF-. Endothelial IL-8, which is secreted from VE cells by
stimulation of IL-1 and TNF- , induces apoptosis in myelogenous
leukemia cell line K562 cells. Monocyte-derived IL-8 could not induce
apoptosis in K562 cells. Moreover, interaction between VE cells and
K562 cells induces the release of endothelial IL-8 from VE cells, and
the attached K562 cells undergo apoptosis. Moreover, 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 significantly inhibits tumor
growth of intraperitoneal and subcutaneous tumor mass of K562 cells and
induces apoptosis in their cells in vivo. Endothelial IL-8 plays an
important role in apoptosis involving endothelial cells, which may
provide us with a new therapy for hematological malignancies.
© 1998 by The American Society of Hematology.
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