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Integrin 2 (CD18)-Mediated Cell Proliferation of HEL Cells on a
Hematopoietic-Supportive Bone Marrow Stromal Cell Line, HESS-5 Cells
Takashi Tsuji,
Iwao Waga,
Katsunari Tezuka,
Masafumi Kamada,
Kimio Yatsunami, and
Hisashi Kodama
From the Division of Hematology, Pharmaceutical Frontier Research
Laboratories Inc, Yokohama, Kanagawa, Japan.
Cellular interactions between hematopoietic cells and stromal cells
play important roles in the proliferation and differentiation of
hematopoietic cells. The proliferation of a human erythroleukemia cell
line, HEL cells, which can differentiate into macrophage- and
megakaryocyte-like cells, and erythroid precursors was dramatically induced on coculture with a hematopoietic-supportive stromal cell line,
HESS-5 cells, which can support long-term hematopoiesis in vitro
without fetal bovine serum. HEL cells proliferated when they were
cocultured with but not without direct cell contact. Because the
coculture supernatants with direct cell contact and cytokines such as
interleukins and growth factors did not exhibit growth-stimulating
activity toward HEL cells, it was suggested that some molecule that has
growth-stimulating activity exists on the surface of the cells.
Extracellular matrix components such as fibronectin, laminin,
vitronectin, and collagen did not affect the proliferation of HEL
cells. An anti-CD18 monoclonal antibody, which recognizes the common
chain of the 2 integrin subfamily, induced dramatic
proliferation of HEL cells. Moreover, the proliferation of HEL cells
was inhibited by an antisense oligonucleotide of CD18 mRNA. As judged
from these observations, the proliferation of HEL cells was mediated by
CD18 molecules expressed on HEL cells. On the contrary, the common
counter-receptor of the 2 integrin subfamily, intercellular adhesion
molecule-1, which is expressed on CHO-K1 cells, did not stimulate the
growth of HEL cells. It is known that other counter molecules of the
2 integrin subfamily, such as complement C3bi and fibrinogen, are
not produced by stromal cells. These findings suggest that the
proliferation of HEL cells may be induced through an interaction
between a novel molecule of the 2 integrin subfamily on HEL cells
and the counter-receptor on HESS-5 cells. The 2 integrin subfamily
may regulate the growth of hematopoietic cells in hematopoiesis in vivo
and/or cause the abnormal growth of leukemia cells.
Blood, Vol. 91 No. 4 (February 15), 1998:
pp. 1263-1271
© 1998 by The American Society of Hematology.

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