2004 Fiscal Year Final Research Report Summary
Study on regulatory mechanism of hematopoiesis by RCAS-1 ; Application in hematopoietic stem cell transplantation.
| Project/Area Number |
14570987
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyushu University |
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Principal Investigator |
MUTA Koichiro Kyushu University, Hospital, Assistant Professor, 大学病院, 講師 (50229928)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Yasunobu Kyushu University, Hospital, Research Associate, 大学病院, 助手 (90304774)
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| Project Period (FY) |
2002 – 2004
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| Keywords | RCAS1 / macrophages / erythroid / progenitors / apoptosis |
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| Research Abstract |
Novel human tumor-associated antigen, RCAS1 (receptor binding cancer antigen expressed on SiSo cells) has been shown to induce apoptosis in normal human erythroid progenitor cells, which express putative RCAS1 receptors. In the present study, we investigated a possible role of RCAS1 produced by human peripheral blood monocytes (CD14 positive cells) and monocyte-derived macrophages. RCAS1 was immunohistochemically detected in cytoplasm of monocytes as well as macrophages. When macrophages were stimulated with LPS, the expression of RCAS1 was remarkably enhanced not only in the cytoplasm but also on the cell membrane. An increased production of RCAS1 mRNA was observed in LPS-stimulated macrophages by quantitative RT-PCR analysis. The soluble RCAS1 molecules were also detected in the culture supernatants obtained from LPS-stimulated macrophages, but not from unstimulated cells. LPS-stimulated macrophages induced cell death of erythroid progenitor cells. This cytotoxic effect was abolished by addition of 22-1-1 monoclonal antibody. These results suggested that macrophages may negatively regulate erythropoiesis through induction of cell death caused in part by RCAS1 molecules. The present findings might also be related to the in-vitro expansion of hematopoietic stem and progenitor cells for transplantation.
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