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Blood, 15 July 2001, Vol. 98, No. 2, pp. 313-321
HEMATOPOIESIS
Receptor binding cancer antigen expressed on SiSo cells, a
novel regulator of apoptosis of erythroid progenitor
cells
Takamitsu Matsushima,
Manabu Nakashima,
Koichi Oshima,
Yasunobu Abe,
Junji Nishimura,
Hajime Nawata,
Takeshi Watanabe, and
Koichiro Muta
From the Department of Medicine and Bioregulatory
Science, Graduate School of Medical Science, Kyushu University,
Fukuoka, Japan; Department of Molecular Immunology, Medical Institute
of Bioregulation, Kyushu University, Fukuoka, Japan; First Department
of Pathology, Fukuoka University, Fukuoka, Japan; and Department of
Clinical Immunology, Medical Institute of Bioregulation, Kyushu
University, Beppu, Japan.
To better understand the control of apoptosis during
erythropoiesis, this study investigated the role of a novel
tumor-associated antigen, RCAS1 (receptor binding cancer antigen
expressed on SiSo cells), with regard to the regulation of apoptosis of
erythroid progenitor cells. Erythroid colony-forming cells (ECFCs)
purified from human peripheral blood were used. Binding experiments of RCAS1 showed that ECFCs abundantly expressed receptors (RCAS1R) for
RCAS1 and that the degree of binding of RCAS1 to the receptors diminished rapidly during erythroid maturation in vitro. When the
soluble form of RCAS1 was added to the cultures, ECFCs underwent apoptosis, including collapse of the mitochondrial transmembrane potential, and activation of caspases 8 and 3. The addition of an
anti-Fas blocking antibody or Fas-Fc failed to reduce the apoptosis induced by RCAS1, thereby indicating that effects of RCAS1 are independent of Fas activation. When binding of RCAS1 to normal bone
marrow cells was analyzed, RCAS1R was evident on cells with an immature
erythroid phenotype (transferrin receptor+/glycophorin
A ) but not with a mature phenotype (transferrin
receptor/glycophorin A+). Histochemical
staining revealed the expression of RCAS1 in the cytoplasm of bone
marrow macrophages. These findings indicate that RCAS1, which is mainly
produced by macrophages in hematopoietic tissue, may have a crucial
role in controlling erythropoiesis by modulating apoptosis of erythroid
progenitor cells via a Fas-independent mechanism.
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