Mechanisms by which chemokine CXCL12 functions in hematopoiesis and lymphopoiesis
| Project/Area Number |
15390160
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAGASAWA Takashi Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (80281690)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2003: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | chemokine / chemokine receptor / bone marrow / homing / hematopoiesis / stem cell / lymphocyte / generative cell |
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| Research Abstract |
CXC chemokine ligand (CXCL)12 (stromal cell-derived factor (SDF-1)/pre-B-cell-growth-stimulating factor(PBSF)) and its primary physiologic receptor CXCR4 are essential for B cell development and colonization of bone marrow by hematopoietic cells during. In this study, we have analyzed further the roles of CXCL12 in mobilization of hematopoietic cells between and within hematopoietic organs. (1)Hematopoietic stem cells(HSCs) are mobile and sequence of hematopoietic colonization events occurs during ontogeny. We have shown that CXCL12 plays a critical role in homing of HSCs and myeloid cells to bone marrow from the peripheral circulation using a long-term repopulation assay and cell homing assay. (2)B lymphocytes are generated from HSCs and develop within bone marrow and dependency on CXCL12 appears at the earliest stages, pre-pro-B cells. We have found that CXCL12-expressing cells are a small population of stromal cells, had several processes, are scattered throughout bone marrow and located some distance from the cells expressing interleukin (IL)-7. Multipotent hematopoietic progenitors are attached to the processes of CXCL12-expressing cells and pre-pro-B cells adjoin their cell bodies. Maturer pro-B cells, which require IL-7, have moved away and adjoin the IL-7-expressing cells. Maturer pre-B cells are not in contact with IL-7-expressing cells. Furthermore, the end-stage B cells, plasma cells again seed CXCL12-expressing cells. Thus, we have identified stage-specific niches for B lymphopoiesis, demonstrated the B lymphocyte characteristic location and movement between specific niches within bone marrow during development and suggested that CXCL12 maintains the precursors in the niche. Together, CXCL12 is likely to play a critical role in the interaction of hematopoictic cells with the specific cellular niches in bone marrow.
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Report
(3 results)
Research Products
(19 results)
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[Publications] Stumm, R., Zhou, C., Ara, T., Lazarini, F, Dubois-Dalcq, M., Nagasawa, T., Hollt, V., Schulz, S.: "CXCR4 regulates interneuron migration in the developing neocortex"J.Neurosci.. 23・12. 5123-5130 (2003)
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[Publications] Ara, T., Itoi, M., Kawabata, K., Egawa, T., Tokoyoda, K., Sugiyama, T., Fujii, N., Amagai, T., Nagasawa, T.: "A role of CXCL12/SDF-1/PBSF and its receptor CXCR4 in fetal and adult T cell development in vivo"J.Immunol.. 170・9. 4649-4655 (2003)
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[Publications] Ara, T., Nakamura, Y., Egawa, T., Sugiyama, T., Abe, K., Kishimoto, T., Matsui, Y., Nagasawa, T.: "Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor (SDF-1)"Proc.Natl.Acad.Sci.USA.. 100・9. 5319-5323 (2003)
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[Publications] Ara, T., Tokoyoda, K.Sugiyama, T., Egawa, T., Kawabata, K., Nagasawa, T.: "Long-term hematopoietic stem cells require stromal cell-derived fadtor-1 for colonizaing bone marrow during ontogeny"Immunity. 19・2. 257-267 (2003)
